The Chicken Major Histocompatibility Complex and Disease

Animal Science Publications Animal Science

1998

The chicken major histocompatibility complex and disease

Susan J. Lamont Iowa State University, [email protected]

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Abstract The chicken major histocompatibility complex (MHC), or B complex, consists of several clusters of highly polymorphic genes, some of which are associated with disease resistance. The class I and class II antigens resemble their mammalian counterparts in the encoded protein structure. The class IV region encodes the B blood group antigens, which are readily identified yb serological blood-typing. The class III region appears to be divided in chickens, with some elements that are MHC-linked and others that map elsewhere. In addition the Rfp-Y system, which bears a strong similarity to the MHC, maps to the opposite side of the nucleolar organiser region on the same microchromosome as the MHC. Each class of MHC genes is a potential candidate for a role in disease resistance. The MHC genes show associations with response to diseases as diverse as virally induced neoplasia, bacterial, parasitic and auto-immune diseases.

Keywords Bacteria, Disease resistance, Fowl, Genetics, Immunity, Major histocompatibility complex, Parasites, Viruses

Disciplines Agriculture | Animal Sciences | Genetics | Immunology and Infectious Disease

Comments This article is published as Lamont, Susan J. "The chicken major histocompatibility complex and disease." OIE Revue Scientifique et echniqueT 17, no. 1 (1998): 128-142. DOI: 10.20506/rst.17.1.1090. Posted with permission.

This article is available at Iowa State University Digital Repository: https://lib.dr.iastate.edu/ans_pubs/855 Rev. sci. tech. Off. int. Epiz., 1998,17 (1), 128-142

The chicken major histocompatibility complex and disease

S.J. Lamont

Department of Animal Science, 201 Kildee Hall, Iowa State University, Ames, Iowa 50011-3150, United States of America

Summary The chicken major histocompatibility complex (MHC), or 6 complex, consists of several clusters of highly polymorphic genes, some of which are associated with disease resistance. The class I and class II antigens resemble their mammalian counterparts in the encoded protein structure. The class IV region encodes the B blood group antigens, which are readily identified by serological blood-typing. The class III region appears to be divided in chickens, with some elements that are MHC-linked and others that map elsewhere. In addition the Rfp-Y system, which bears a strong similarity to the MHC, maps to the opposite side of the nucleolar organiser region on the same microchromosome as the MHC. Each class of MHC genes is a potential candidate for a role in disease resistance. The MHC genes show associations with response to diseases as diverse as virally induced neoplasia, bacterial, parasitic and auto-immune diseases.

Keywords Bacteria - Disease resistance - Fowl - Genetics - Immunity - Major histocompatibility complex - Parasites - Viruses.

(GVH) splenomegaly (62), GVH-chorioallantoic membrane Discovery of the chicken major pocks (135) and the mixed lymphocyte reaction (100). histocompatibility complex Unique genetic structure of the The B complex (or major histocompatibility complex: MHC) of the chicken was first reported by Briles et al. as a highly chicken major histocompatibility polymorphic erythrocyte antigen or blood group system (13). The gene locus symbol was assigned as B to indicate that this complex region was the second chicken blood group system to be discovered. Gilmour independently reported the discovery of the same Pink et al. defined a three-locus model of the chicken MHC blood group locus (45). Persistence of multiple alleles of the B (118). In the ensuing two decades, the molecular dissection of system, even in small, closed and inbred populations, the chicken MHC has demonstrated an unanticipated level of suggested a role of the B blood group in fitness and a selective complexity of genomic organisation (Fig. 1) (50, 51, 52, 65, advantage of B heterozygosity for survival (12, 45). The 67, 79, 101). Bloom and Bacon assigned the MHC to discovery by Schierman and Nordskog that the B blood group microchromosome 16 by analysing aneuploid chickens which system is linked to the major histocompatibility complex bore the nucleoli organiser region (NOR) on the extra determined the biological mechanism by which the B system chromosomes (8, 9). This microchromosome was estimated influenced fitness (134). In skin graft experiments using to be 8 megabase pairs (Mbp), with 6 Mbp of NOR encoding partially inbred birds, grafts between birds of the same B type approximately 400 tandemly repeated ribosomal RNA (rRNA) were accepted while those of different B blood types were clusters (33,124). rejected, thus the linkage of B with the major skin graft locus was confirmed. Additional evidence that the B system The genomic organisation of the chicken MHC differs from represented the chicken MHC was provided by the that of a typical mammalian MHC. The chicken MHC is quite identification of B as the locus controlling graft versus host compact, approximately 30 to 100 kilobase (kb) long Rev. sci. tech. Off. int. Epiz., 17 (1) 129

rRNA : ribosomal RNA cM : centiMorgan

Fig. 1 Schematic presentation of organisation of the chicken major histocompatibility complex Modified from Kaufman & Lamont (72) .

compared to up to 4 Mbp in mammals, and the number of Research conducted by W.E. Briles and M. Miller showed that genes in MHC-like multigene families is therefore relatively some class I a and class II (3 bands on Southern blots do not small (approximately 2 class II (3,1 class II a and 1-2 class I a co-segregate with the serologically defined B complex. This genes) (63, 71). The few class I a genes located in cosmid new locus, defined by restriction fragment length cluster I, which are the only genes to encode polymorphic polymorphism (RFLP) analysis, was named the Rfp-Y locus molecules expressed at a high level, represent the classical (16). The Rfp-Y locus was mapped to cosmid cluster II/IV and MHC (the B-F/B-L locus) of the chicken. Other genes, such as III (106), separated from cosmid cluster I by the highly the TAP (transporters associated with antigen processing) recombinogenic region of the repetitive NOR (108). By in situ gene(s) involved in transport of antigenic peptides across the hybridisation, both the B and Rfp-Y complexes were mapped membrane of the endoplasmic reticulum for association with to the same microchromosome (42). The Rfp-Y region is class I molecules, are also located in the classical MHC region. thought to be involved in natural killer recognition, based on Non-classical (non-class I, non-class II) MHC genes mapping the involvement of class I and animal C-type lectin (such as to this region include the 12.3 gene that encodes for a G the 17.8 gene) molecules (107). protein-like molecule (52), the 8.5 gene that encodes a B-G molecule (68), the 21.7 gene that encodes a TAP molecule The ß m cDNA clones (the ß m protein being associated with (J.F. Kaufman and N. Bumstead, unpublished findings), as 2 2 well as the 17.8 gene that encodes a member of the C-type mature class I MHC molecules [115]) were identified by animal lectin super-family (7). screening with oligonucleotides based on protein sequence.

Using these cDNAs as probes, a single (ß2m gene located outside the MHC was found (69). The ß m gene was located The distribution of class III genes in the chicken may include 2 by in situ hybridisation on a non-MHC microchromosome non-MHC linked sites. Most genes characteristic of the (124). mammalian class III region have not been identified in the chicken MHC cosmids isolated thus far. Electrophoretic polymorphisms of glyoxalase 1 (GLO) (126) and chicken Genes encoding the MHC class IV, or B-G, erythrocyte factor B (78) do not segregate with the B complex. However, a alloantigens are closely (approximately 0.05 centiMorgan DNA polymorphism, detected by G9a (109), of the class III [cM]) linked to the B-F/B-L region (31, 138). Several groups region of the human MHC has been mapped to the chicken have isolated cDNA clones corresponding to B-G molecules MHC (140), providing evidence that at least some part of the (37,47, 64, 65, 68). The B-G genes map to cosmid clusters V class III region is associated with the chicken MHC. and VI. Based on Southern blots using these cDNA clones as 130 Rev. sci. tech. Off. int. Epiz., 17 (1)

probes, the B-G genes form an extensive multigene family identified on cluster I; two class II (3 gene fragments and two (106). One B-G RFLP corresponds to the 8.5 gene in cosmid class I a gene fragments and the 17.8 gene were identified on cluster I, which encodes a B-G molecule found on B cells (64, cluster II/IV; and a class II ßgen e fragment, the 13.8 gene and 67). some rRNA genes were identified on cluster III (49). Researchers later determined that only cluster I corresponds The map of the MFIC from CB chicken cosmids provides a to the serologically defined B complex. good model for an understanding of the chicken MHC (Fig. 1). However, RFLP using class I a, class II ß and B-G Class II (3 genes, pseudogenes and cDNAs from several probes on DNA of other lines have suggested gene expansion chicken strains have been described (11, 113, 143, 162, 165, and contraction (23, 24, 90, 92, 93, 103, 119, 147, 157). 166). Apparently, there are extra class I a genes in the B21 haplotype, which is known to be associated with Marek's Several class II a cDNAs have also been isolated (70). disease resistance (23, 103). Kaufman et al. identified the major class II a cDNA by using degenerate oligonucleotide polymerase chain reaction (PCR) The use of DNA analysis to provide biochemical based on the protein sequence. Using this cDNA as a probe, characterisation of the existing variation in the MHC is a the gene was found to co-segregate with neither the valuable addition to serological analysis. By using DNA B complex nor the Rfp-Y locus in the F2 family described by analysis, sub-regions and genotypes for which the production Briles, but was located about 5 cM away from the B complex of serological reagents has failed can be examined, MHC in the Compton reference family (70). The a chain cDNAs chromosomal recombinants can be analysed and newly have an al domain, an a2 immunoglobulin (Ig)-like domain, identified genotypes can be categorised. A standard a transmembrane domain and a short cytoplasmic tail. The nomenclature should be defined for DNA polymorphisms of sequences and analysis of the B-L antigen (48) demonstrate MHC haplotypes, as has been defined for serological analysis the B-L to be a typical class II MHC molecule. (14). The chicken MHC class II (3 genes are organised similarly to those of mammals, with an exon encoding the signal sequence, a polymorphic ß1 PBR domain, a non-polymorphic Class I (B-F)and class II (B-L) ß2 Ig-like domain, a transmembrane domain and two cytoplasmic exons, the last including the 3' UT. Based on genes and antigens sequences of several haplotypes, there seem to be three isotypes of class II |3 genes. The two class II (3 genes (B-LBI and Multiple chicken class I a cDNAs, one class I a gene and II) in cluster I are closely related and highly expressed. The several chicken ß2m cDNAs have been described, as well as two genes located on cosmid cluster II/IV (Rfp-LIII and V) and class I and ß2m proteins from erythrocytes (49, 69, 80, 110, the gene on cosmid cluster III (B-LBIV) are quite different 124,159). The chicken B-Fct chain gene is organised similarly from the cluster I genes, but are virtually identical to each to mammalian classical class I genes, with an exon encoding other and are poorly expressed. Other class II (3 sequences the signal sequence, three exons (al, a2 and a3) encoding (named B-LBVÍ) form a third group. the extracellular domains, an exon encoding the transmembrane (TM) region and three exons encoding the The chicken MHC has many features which contrast with cytoplasmic tail and 3' UT (untranslated region). The ß m 2 those of mammals. The genes are very rich in guanine + gene shows a similar organisation to mammalian ß m genes, 2 cytosine (G 4- C) compared to the mammalian counterparts, with one exon for the signal sequence, another exon for most and this is particularly true for some promoters, exons and of the protein, one for the last four amino acids of the protein introns. The promoters for class I a, class II (3, and ß2m genes and part of the 3' UT, and the last exon for the remaining part have G 4- C-rich regions near the transcription initiation site of 3' UT. Only one class I gene product seems to be expressed instead of the typical mammalian TATA boxes, and also have at high levels on chicken blood and spleen cells: of the six CB X and Y boxes, which are expected for class II (3 - but not class cosmid fragments that hybridised with the class I a cDNA I a or ß2m - genes. The promoters of class I a and ß2m also F10, only one (B-FIV of cosmid cluster I) hybridised with an contain interferon response elements (IRE). The sequence oligonucleotide from the 3' UT (49). differences may lead to important functional differences between chicken and mammalian MHC genetic regulatory In the initial cloning of the chicken MHC, a chicken MHC elements. class II ß pseudogene was isolated by cross-hybridisation with a human class II |3 cDNA (11) and used to isolate cosmids Understanding the functional activity of chicken MHC 12 from a DNA library of a CB (B ) chicken. These cosmids regulatory elements will be important for the modulation of overlapped into four clusters, two of which were later gene expression levels and, thereby, MHC function. The connected by an overlapping lambda genomic DNA clone. conserved IRE in the chicken MHC class I promotor region Two class II (3 gene fragments and four class I a genes were has been shown to induce gene expression (164). Chen et al. Rev. sci. tech. Off. int. Epiz., 17(1) 131

characterised a functional chicken MHC class II gene promoter as a 0.7 kb chicken DNA fragment that contains a The chicken major functional promoter, but may require additional enhancer(s) histocompatibility complex and outside this immediate 5' upstream region for efficient initiation of transcription (25, 26). Deletion analysis of this immune reponse DNA fragment revealed a short fragment in the 3' end that was crucial for the promoter function, and negative regulatory Regulation of cellular communication in the immune elements located further upstream. Surprisingly, the response is a critical function of the chicken MHC (34). The conserved MHC class II X and Y boxes did not have a MHC cell-surface proteins distinguish 'self from 'nonself. significant influence on promoter activity when transfected in This allows immune reaction to occur against foreign antigens a macrophage cell line. Recent studies show protein-DNA of a virtually infinite variety while simultaneously preserving binding of the Y box with nuclear extracts of lymphocyte, but the self-integrity of the organism. The MHC cell-surface not macrophage, cell lines (Y. Chen, S. Carpenter and molecules interact with both the foreign antigen and with S.J. Lamont, unpublished findings). The involvement of complementary structure of other immune cells, thereby interferon, ETS-related proteins and other factors involved in generating an immune response that is specific for the the regulation of this promoter were suggested by sequence inducing antigen. analysis. Glucocorticoids decreased interferon-induced gene expression (26). Cells of the immune system must share at least one MHC haplotype to communicate effectively; this phenomenon is known as MHC restriction. The MHC restriction may function at the level of interactions between mature cells in Class IV (B-G) genes and the immune response or at immune cell differentiation (149, 151, 152). The T-/B-cell co-operation necessary for antibody antigens production and for the generation of germinal centres in the spleen requires identity at the MHC (146). The interaction of The MHC class IV (B-G) molecules were initially studied antigen-presenting cells and T cells, evaluated by the in vitro because of their extensive serological polymorphism, which proliferation of T cells in response to specific antigen in the could contribute to the active search for correlated functional presence of antigen-presenting cells, is also MHC-restricted. variation in biological traits. The availability of alloantibodies The B-F/B-L antigens are the restriction elements for all of to B-G antigens on erythrocytes enabled the discovery of the these cellular interaction phenomena (150, 153). chicken MHC. B-G proteins, cDNAs and genes have been examined (67, 68, 104, 105). In addition, the whole B-G The cytotoxic reactions of T cells with some virus-infected region and a B-G gene expressed on B cells are linked to and/or transformed cells are MHC-restricted (99, 132). An cosmid cluster I. There are multiple B-G molecules present on antigen-restricted class II-positive T cell with cytotoxic erythrocytes, and very similar molecules are present on properties was identified as the effector cell responsible for the thrombocytes, lymphocytes, and on stromal cells of the caecal MHC-restricted cell-mediated cytotoxicity (158). Cytotoxic tonsil, bursa, thymus and the epithelial cells of the small cells which are MHC- and virus-restricted may be an intestine (65, 77, 105, 128). The erythrocyte-surface B-G important immune surveillance mechanism for preventing molecules are generally disulphide-linked dimers (66, 77, the proliferation of virally induced tumours (137). 102,118,127). These B-G chains vary significantly in size (35 to 55 kiloDaltons [kDa]) depending on the length of the The MHC has widespread effects on genetic control of immuno-responsiveness, either due to its role as a restriction cytoplasmic tails. The B-G molecules on stromal cells in the element or through specific MHC-linked immune response bursa, thymus, caecal tonsil and on small intestine epithelial genes. Antibody production against a variety of antigens, such cells are larger than the erythrocyte B-G molecules (65, 77, as immune response to synthetic polypeptides, islinke dt o the 127,128). chicken MHC (6, 54, 112). Antibody titres to several soluble antigens (e.g., bovine serum albumin: BSA), to viral antigens While the true functions of B-G molecules are not yet known, (3) and to cellular antigens (e.g., Salmonella Pullorum their structure suggests that these are typical adhesion bacterin, sheep erythrocytes) (98, 111) are also associated molecules, with the extracellular region involved in with the chicken MHC. Total serum IgG levels are also under interactions with other cells or with the environment and the genetic control by the B complex (123). cytoplasmic tail involved in signal transduction. The polymorphism may help the molecules respond to a wide Genetic control of immuno-reponsiveness linked to the range of stimulating molecules. The B-G molecules exhibit chicken MHC has also been shown in assays of cell-mediated specific immune phenomena (including an 'adjuvant effect', immunity. The delayed wattle reaction is commonly used as a which initiates a rapid and strong antibody response) and the measure of cell-mediated immunity in the chicken (76). Both presence of natural antibodies (55, 67, 97, 129, 136). polyclonal activators of T cells, such as phytohaemagglutinin 132 Rev. sci. tech. Off. int. Epiz.. 17 (1)

(144), and specific inducers, such as Staphylococcus aureus Table I (an important pathogen of poultry) (28), show cell-mediated Selected diseases for which an association of resistance or severity is found with the chicken major histocompatibility complex immune responses associated with the B complex.

Type of disease Disease Complement proteins are extremely important in the immune reaction as a means to destroy invading pathogens. The levels Neoplastic diseases (virally induced) Marek's disease neoplasia of total serum haemolytic complement have been associated Marek's disease transient paralysis Rous' sarcomas with the MHC in chickens (22). Lymphoid leukosis Bacterial diseases Staphylococcus aureus Qureshi et al. showed that the chemotactic activity of chicken Fowl cholera (Pasteurella multocida) Salmonella Enteritidis blood mononuclear leucocytes and the activity and Parasitic diseases (coccidiosis) Eimeria tenella recruitment to the peritoneal cavity of macrophages varied Eimeria acervulina among B-congenic lines, which differ from each other only in Autoimmune diseases Autoimmune thyroiditis the microchromosome (or a fraction of it) which bears the Vitiligo MHC (121, 122). Chicken B-congenic lines were also used to demonstrate MHC associations with cell-surface CD4 (cluster of differentiation antigen 4) and CD8 lymphocyte percentages and ratios (56).

The most intensively investigated association of the MHC The MHC has been studied in chicken lines selected for with resistance to a specific disease concerns Marek's disease various traits of immunoresponsiveness, for example, in (MD), a herpesvirus-induced lymphoma. The emergence of experiments to measure long-term selection for antibody increasingly virulent strains of MD virus (MDV) ensures response to sheep red blood cells. Correlated changes of MHC continued high levels of interest in the use of genetic allelic frequencies with the antibody selection occurred (39, resistance approaches to this disease (17). Using MHC 117). Although MHC genotype explains part of the variation recombinants to the B-F/B-L region (15, 60), partial MHC in antibody levels, the background genome also had a control has been mapped. The MHC is associated with substantial effect (40, 116). After divergent selection for early MD-related traits of incidence of tumour formation, mortality antibody response to Escherichia coli vaccination in meat-type and transient paralysis induced by MDV. The haplotype B21 chicken lines, differences in the frequency of MHC class IV conveys MD resistance to many different genetic RFLP bands were present (148). Although the MHC class IV backgrounds. Variation in response to MDV by sublines that are identical at the B locus, however, illustrates the influence differences did not persist to large measure in the F2 generation, RFLP bands of class I and TAP2 clones were of non-MHC genes on response to MD (2, 3). An interesting- associated with the antibody response (21). In Leghorn lines and currently conflicting - picture is emerging for the role of selected divergently for an index of immunocompetence traits the Rfp-Y region in resistance to MD. Although two studies (antibodies, cell-mediated response and reticuloendothelial found no association between Rfp-Y variation and resistance to the disease (82, 154), one study found that birds of activity) (27), differences occurred in MHC genotype homozygous Y3 genotype carried more than twice the risk of frequencies identified both by serology (73) and by DNA tumour development than the other pooled genotypes (156). analysis of class II (N. Lakshmanan and S.J. Lamont, The differences between studies probably result from the unpublished findings), and class IV (S. Weigend and specific Rfp-Y alleles and background genes used, as well as S.J. Lamont, unpublished findings). Many diverse facets of the the MDV strain used for challenge and the recorded disease immune response, therefore, are partly under MHC genetic traits. A recent study which used a genome-wide search for control. quantitative trait loci has identified several which affect resistance to MD (155). Genetic complementation of MHC alleles with other genes, such as Ir-GAT (141) and the The chicken major background genome (57), affects susceptibility to Marek's disease. The MHC also influences the response to other virally histocompatibility complex and induced diseases, including Rous' sarcoma virus tumours (137) and avian leukosis (163). disease resistance In addition to virally mediated diseases, other categories of The association of the chicken MHC with resistance to disease disease have also been demonstrated to be associated with the has motivated studies of both the basic biology and the MHC (2, 43). These include fowl cholera (88), obese strain practical application of knowledge of the chicken MHC. spontaneous autoimmune thyroiditis (125) and coccidiosis These studies have been summarised in several recent reviews (19, 94). MHC congenic lines have played an important role (2, 43, 72, 83, 84, 85, 87,142) (Table I). in defining MHC associations for diseases as diverse as Rev. sci. tech. Off. int. Epiz., 17(1) 133

Marek's disease (4, 133), tumours induced by Rous' sarcoma (12, 45) (Table II). Economically important traits, such as virus (160) and v-src (145), and Staphylococcus aureus (29). juvenile and adult mortality, body weight, fertilisation rate, The range and variety of diseases influenced by the chicken embryonic mortality, hatchability and egg production are MHC is, therefore, extensive. influenced by MHC genotype (2, 35, 130). Several independent studies have shown that long-term selection for There is genetic variability for resistance against various egg production traits and disease resistance have significantly diseases in poultry populations, yet selection for fitness and altered MHC allelic frequencies (44, 81, 89,139). From these viability is one of the more difficult tasks for breeders who use selection studies, B2 and B21 appeared to show overall only conventional genetic selection methods. Avian leukosis beneficial associations with economic traits in chickens. A and Marek's disease are two successful examples of the variety of other studies have demonstrated MHC associations application of genetic selection for resistance to specific with particular production traits but no consistency of specific diseases. Convincing evidence also exists for a genetic MHC haplotypes or associated traits (1, 41, 74, 75, 131). component to resistance to Salmonella in chickens. Two groups have examined resistance to Salmonella Enteritidis in several genetic lines and have found variation in the lethal dose 50%, in organ contamination and in bacterial burden Table II (18, 20, 53, 120). In recent reports, several natural Selected production traits for which an association with the major resistance-associated macrophage protein-1 (Nramp l)-linked histocompatibility complex is found markers were examined and two were identified to be associated with splenic bacterial burden three days after Production traits intravenous inoculation of Salmonella Enteritidis (46). The Body weight possibility that Nramp1 also influences infection by natural Juvenile survival routes of exposure and in other lines of chickens remains to be Adult survival determined. Reports so far present conflicting results Egg production regarding the MHC role in resistance to Salmonella, thereby Hatchability illustrating the need for detailed analysis of this relationship. Embryonic mortality Recent studies have shown an association of Nramp1 with Fertilisation rate differential resistance to Salmonella Typhimurium infection (61) and of the MHC with 5. Enteritidis infection-induced morbidity and mortality (30). In both studies, the lines examined were derived from backgrounds related to egg-production type stock. Birds which were aneuploid (trisomic) for the MHC-bearing chromosome were used to map the MHC to No haplotype performs optimally in all genetic backgrounds microchromosome 16 and to examine the effects of MHC in response to all disease challenges. This is not surprising, gene dosage on several biological systems. The chicken MHC given the many different immune mechanisms involved in (B complex) and the NOR were shown to be linked on resistance to each specific disease and the many levels at microchromosome 16 (8, 38). The excess rRNA genes in which genetic control is exerted by the MHC. The repeated aneuploid birds appear to be inactivated, but the MHC genes association of disease resistance with the MHC, but not with are expressed in a relatively dose-dependent fashion. one specific MHC haplotype, suggests an important role for Aneuploid chickens have both a greater concentration of non-MHC genes located within the complex. Specific erythrocyte cell-surface MHC glycoproteins than disomic resistance gene identification and the use of genetic chickens (9) and an increased amount of B-L antigen on engineering may allow the construction of resistant bursal cells (32) and macrophages (95). The dosage of MHC haplotypes that have not been produced by conventional genes also alters primary immune organ development, thus breeding. aneuploid chickens have smaller bursae and thymuses and a reduced number of lymphocytes (59). Aneuploid macrophages exhibited a cell-contact-dependent increase in killing tumour target cells (96). The expression of extra MHC The chicken major copies has important implications for the feasibility of producing chickens by utilisation of natural variation or histocompatibility complex and genetic engineering techniques, with increased copy numbers of the MHC genes to enhance health or production production traits characteristics (10, 83). Because many traits for disease resistance associated with the MHC are dominant traits (43), The B complex has been associated with genetic variation in an individual with extra MHC gene copies may be resistant to production traits, such as general mortality, for many years a greater variety of diseases. 134 Rev. sci. tech. Off. int. Epiz., 17 (1)

Applications of knowledge of misclassifying the allelic forms caused by recombinations between the serologically determined class IV genes (B blood the major histocompatibility group) and the class I and II genes (and additionally the MHC-linked, non-class 1, non-class II genes, such as TAP2 complex in the poultry industry and the unique Rfp-Y region). Initial work has begun to address the need for economic technologies capable of Knowledge of the chicken MHC and the impact of this defining the genotype of large sample numbers (58). The complex on the avian immune system is now at a sufficient current understanding of the genetic regulatory elements of level for manipulation of the MHC to be used to integrate the MHC is minimal. The factors controlling gene expression immune systems management into poultry production must also be understood to selectively enhance expression. As systems (36). Industrial use of MHC information in chickens the allelic diversity of each individual class of MHC genes is occurs in two main areas. The first use is for pedigree defined, the relationships of variation in structural genes and confirmation. As a result of the enormous number of eggs and regulatory elements with disease resistance must be chicks that may be handled simultaneously at a hatchery and determined. the practice of separating hens from progeny, even a very small percentage of pedigree errors could result in large numbers of incorrectly pedigreed chicks. Line-specific genetic markers can be used to assure purity of lines. Blood group Conclusions antigens, including the B blood group, are excellent candidates for use as genetic markers because such antigens Genetic selection for the MHC is a desirable approach to are highly polymorphic and are quickly and cheaply improving immunoresponsiveness and disease resistance (86, identifiable from a small blood sample. 87, 91). Although the progress per generation may be small, such progress is heritable and therefore the increments are Another contemporary application of MHC information is as a cumulative over time. Understanding MHC-disease means of altering MHC allelic frequencies selectively to associations can allow genetic selection to be performed by improve correlated traits (primarily disease resistance and marker-assisted selection, rather than by direct challenge of vaccine response). Marek's disease vaccination efficacy in populations with disease agents. This avoids the high costs, commercial genetic backgrounds has been associated with the labour and animal welfare concerns associated with pathogen MHC alleles (5). Beneficial MHC alleles can be increased in challenges. The resulting enhanced immunoresponsiveness frequency or fixed within a grandparent line. The extreme conserves natural resources by decreasing the production polymorphism of the MHC (over 50 allelic forms in Leghorns, losses that are due to disease. In addition, both animal welfare more in meat-type birds) gives many options for choice of and food safety are enhanced by producing genetic stocks specific B alleles in grandparent lines and various which possess greater resistance to disease pathogens. heterozygous combinations at the commercial crossbred level. The interaction of MHC alleles with the background genome, however, is an important practical consideration.

New biotechnologies should be incorporated into new industrial applications of MHC manipulation (85, 87). As antigen-binding specificity is critical to effective poultry vaccine design, detailed knowledge of specific MHC types in a population would allow specific choices to optimise the vaccine-host MHC combination or would allow the design of targeted recombinant vaccines (5, 114, 132, 161). The DNA can be examined directly for allelic forms of the MHC genes of each class with the use of specific gene probes. Direct analysis of class I and II genes will avoid the possibility of Rev. sci. tech. Off. int. Epiz., 17(1) 135

Complexe majeur d'histocompatibilité chez les volailles et maladie S.J. Lamont

Résumé Le complexe majeur d'histocompatibilité chez les volailles (CMH) ou complexe B comporte plusieurs groupes de gènes très polymorphes, dont certains sont associés à la résistance aux maladies. Les antigènes des classes I et II présentent des similitudes avec ceux des mammifères pour ce qui est de la structure protéique codée. La région de la classe IV code pour les antigènes du groupe sanguin B, qui sont facilement identifiés partypage sérologique. La région de la classe III semble être divisée chez les volailles, certains éléments étant liés au CMH et d'autres localisés ailleurs. De plus, le système Rfp-Y, qui présente une grande similitude avec le CMH, apparaît à la cartographie localisé du côté opposé par rapport à la région de l'organisateur nucléolaire sur le même micro chromosome que le CMH. Chaque classe de gènes CMH pourrait jouer un rôle dans la résistance aux maladies. Les gènes du CMH présentent des associations avec la réponse à des maladies aussi différentes que les néoplasies d'origine virale, les maladies bactériennes, parasitaires et auto-immunes.

Mots-clés Bactéries - Complexe majeur d'histocompatibilité - Génétique - Immunité - Parasites - Résistance aux maladies - Virus - Volailles.

Enfermedad y complejo mayor de histocompatibilidad en el polio S.J. Lamont

Resumen El complejo mayor de histocompatibilidad (major histocompatibility complex, MHC), o complejo B en el caso del pollo, consiste en varios racimos de genes extremadamente polimórficos, algunos de los cuales están relacionados con la resistencia a la enfermedad. Los antígenos de la clase I y la clase II se asemejan a sus homólogos mamiferianos en cuanto a su estructura proteica codificada. La región de la clase IV codifica a los antígenos determinantes del grupo sanguíneo B, que pueden identificarse fácilmente portipificación serológica de la sangre. En el pollo, la región de la clase III parece hallarse dividida, con algunos elementos ligados al MHC y otros que aparecen cartográficamente en otros lugares. Además, el sistema Rfp-Y, que presenta una gran similitud con el MHC, aparece cartográficamente en el lado opuesto a la región organizadora nucleolar, en el mismo microcromosoma que el MHC. Todas las clases de genes MHC son susceptibles de desempeñar algún papel en la resistencia a la enfermedad. Los genes del MHC están relacionados con la respuesta a varias enfermedades, desde las neoplasias inducidas por virus hasta las enfermedades de origen bacteriano o parasitario o las enfermedades autoinmunes.

Palabras clave Bacterias - Complejo mayor de histocompatibilidad - Gallina - Genética - Inmunidad - Parásitos - Resistencia a la enfermedad - Virus. 136 Rev. sci. tech. Off. int. Epiz., 17 (1)

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