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Sequence and Genes of the B Locus Lee D Defining the Turkey MHC: Sequence and Genes of the B Locus Lee D. Chaves, Stacy B. Krueth and Kent M. Reed This information is current as J Immunol 2009; 183:6530-6537; Prepublished online 28 of September 29, 2021. October 2009; doi: 10.4049/jimmunol.0901310 http://www.jimmunol.org/content/183/10/6530 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2009/10/28/jimmunol.090131 Material 0.DC1 References This article cites 61 articles, 14 of which you can access for free at: http://www.jimmunol.org/content/183/10/6530.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists by guest on September 29, 2021 • Fast Publication! 4 weeks from acceptance to publication *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2009 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Defining the Turkey MHC: Sequence and Genes of the B Locus1,2 Lee D. Chaves,3 Stacy B. Krueth, and Kent M. Reed The MHC, the most polymorphic and gene dense region in the vertebrate genome, contains many loci essential to immunity. In mammals, this region spans ϳ4 Mb. Studies of avian species have found the MHC to be greatly reduced in size and gene content with an overall locus organization differing from that of mammals. The chicken MHC has been mapped to two distinct regions (MHC-B and -Y) of a single chromosome. MHC-B haplotypes possess tightly linked genes encoding the classical MHC molecules and few other disease resistance genes. Furthermore, chicken haplotypes possess a dominantly expressed class I and class II B locus that have a significant effect on the progression or regression of pathogenic disease. In this study, we present the MHC-B region of the turkey (Meleagris gallopavo) as a similarly constricted locus, with 34 genes identified within a 0.2-Mb region in near-perfect synteny with that of the chicken MHC-B. Notable differences between the two species are three BG and class II B loci in the turkey Downloaded from compared with one BG and two class II B loci in the chicken MHC-B. The relative size and high level of similarity of the turkey MHC in relation to that of the chicken suggest that similar associations with disease susceptibility and resistance may also be found in turkey. The Journal of Immunology, 2009, 183: 6530–6537. he MHC is a genomic locus found in all jawed vertebrates genes for class I, class II A, and class II B genes (11), the chicken (Gnathostomes) and is a key component in immune re- BL-BF locus lacks many immune genes present in mammal MHCs http://www.jimmunol.org/ T sponse. Originally identified through tissue graft rejection (compliments, cytokines, and so on) and contains only two MHC experiments, the MHC locus has subsequently been found to con- class I and two class II B genes within 50 kb (12, 13). Chicken tain several classes of genes responsible for Ag presentation to the MHC-B haplotypes predominantly express a single class I and host immune system. Specifically, classical MHC molecules en- class II B transcript, thereby reducing the diversity of Ags pre- coded within the MHC possess a highly polymorphic peptide- sented (14, 15) and have been described as a “minimal essential binding groove to bind peptide Ags through hydrophobic and/or MHC.” A single monomorphic class II A gene located 5 cM from hydrogen bonding and present them to T cell receptors. The MHC the BF-BL region encodes a protein that will dimerize with either class I A genes are expressed in all nucleated cells, interacting with class II B product to form the class II molecule (16). Interestingly, ␤ by guest on September 29, 2021 2-microglobin to present mostly endogenously generated pep- unlike mammals, the chicken has two C-type lectin-like genes, one tides of nine amino acids. MHC class II molecules are het- of which is quite similar to NK complex loci (17). The limited erodimers (␣ and ␤ genes) primarily expressed on APCs (dendritic repertoire of MHC molecules in the chicken—and the Ags they are cells, B cells, and macrophages) and present mostly exogenously able to present—has a remarkable effect on the species’ ability to derived peptides of ϳ9–11 aa. resist/resolve infectious disease including bacteria, viruses, and The chicken MHC has been defined as two genetically unlinked parasites (18–20). clusters, the MHC-B and -Y loci, located with the nucleolar orga- Studies of the closely related quail have identified an expanded nizer region on the same microchromosome (GGA16) (1–5). The set of MHC genes occupying the same genome locus (21). Similar Y locus contains lectin-like and nonclassical MHC genes with var- to the chicken, expression was unequal between quail MHC class ied effects on disease susceptibility (6–9). At least one class I-like I and II loci within haplotypes (22). Studies in non-Galliform avian locus is polymorphic and transcribed (10). The chicken MHC-B is species have identified greater numbers of class I and class II B subdivided into two regions, the BG and the BL-BF. The BL-BF alleles within individuals compared those seen in the turkey and region contains the classical class I and class II B genes. In contrast chicken, suggesting the presence of additional loci (23–26). to mammalian genomes, which contain on average six paralogous Recent work (27) in the turkey has identified two MHC regions homologous to the chicken B and Y loci. Bacterial artificial chro- mosome (BAC)4 clones containing portions of these regions were Department of Veterinary and Biomedical Sciences, College of Veterinary Medicine, University of Minnesota, St. Paul, MN 55108 physically mapped to turkey metaphase chromosomes through flu- Received for publication April 24, 2009. Accepted for publication September orescent in situ hybridization and genetically mapped by segrega- 15, 2009. tion analysis using a resource population. Like the chicken, these The costs of publication of this article were defrayed in part by the payment of page two regions were genetically unlinked and located on the same charges. This article must therefore be hereby marked advertisement in accordance nucleolar organizer region-containing microchromosome (27). with 18 U.S.C. Section 1734 solely to indicate this fact. Separated by an estimated 50 million years (28), the genomes of 1 This research was supported by grants from the University of Minnesota Agri- the turkey and chicken have been shown to be highly homologous; culture Experiment Station and the Cooperative State Research, Education, and Extension Service, U.S. Department of Agriculture (2004-35205-14217 and 2009-35205-05302). 2 The sequence(s) presented in this article has been submitted to GenBank (www. 4 Abbreviations used in this paper: BAC, bacterial artificial chromosome; EST, ex- ncbi.nlm.nih.gov/GenBank) under accession number(s) DQ993255. pressed sequence tag; LAAO, L-amino acid oxidase; TRIM, tripartite motif; UTR, 3 Address correspondence and reprint requests to Dr. Lee D. Chaves at the current untranslated region. Address: National Jewish Health, Division of Allergy and Clinical Immunology, De- partment of Medicine, Denver, CO 80206. E-mail address: [email protected] Copyright © 2009 by The American Association of Immunologists, Inc. 0022-1767/09/$2.00 www.jimmunol.org/cgi/doi/10.4049/jimmunol.0901310 The Journal of Immunology 6531 Downloaded from http://www.jimmunol.org/ by guest on September 29, 2021 FIGURE 1. Sequence features of the turkey MHC-B region. A, BACs containing the MHC-B region of the turkey and the additional region amplified by PCR. B, GC content plot of the turkey MHC calculated by continuous 100-bp windows. C, Positions of repetitive elements. D, tRNAs present in the turkey MHC. E, Genes and orientation predicted within the turkey MHC-B. Black arrows denote CpG islands. F, The homologous chicken sequence is provided for comparison. chromosomal markers are generally present in both species in syn- clone from the library (97E05) containing a portion of the MHC-B region tenic order (29). Gene sequence studies have found most coding was isolated previously (27). Screening for additional BAC clones was and predicted amino acid sequences to be Ͼ90% identical (30, 31). performed as previously described (33) using overlapping oligonucleotide probes based on the end sequences of clone 97E05 (GenBank accession However, little is known of the similarities between the two spe- nos. DX922434-5), as well as a PCR product corresponding to the CD1.1 cies at the most variable region of the vertebrate genome, the gene (GenBank accession no. EU522671) of the turkey (29). Additional MHC. This work was undertaken to describe the core MHC se- BAC clones were identified and end sequencing of these clones (GenBank quence of the turkey and to compare this most variable genome accession nos. ET222701-4) anchors them within the 97E05 clone with Ј region to homologous sequences derived from other avian species. additional sequence extending further into the 5 BG region (positions are based on the most recent sequence map of the chicken MHC (34), with “5Ј” The resources available for the chicken (whole-genome sequence, and “upstream” referring to the “BG2-3” region and “3Ј” and “down- multiple MHC haplotype sequences, and close phylogenetic rela- stream” referring to “CD1A1-2” region).
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