Allotype Suppression and Epitope-Specific Regulation Leonore A
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Levels, B-1 and B-2 Cells, and Antibody Responses Ir Allotype Heterozygous F1 Mice ANN MARIE HAMILTON and JOHN F
Developmental Immunology, 1994, Vol 4, pp. 27-41 (C) 1994 Harwood Academic Publishers GmbH Reprints available directly from the publisher Printed in Singapore Photocopying permitted by license only Effects of IgM Allotype Suppression on Serum IgM Levels, B-1 and B-2 Cells, and Antibody Responses ir Allotype Heterozygous F1 Mice ANN MARIE HAMILTON and JOHN F. KEARNEY" Division of Developmental and Clinical Immunology, Department of Microbiology, University of Alabama, Birmingham, Alabama 35294 IgM allotype heterozygous F1 mice were independently suppressed for Igh6a or Igh6b to evaluate the contribution of B-1 and B-2 cells to natural serum IgM levels and Ab responses. B-2 B cells expressing IgM of the suppressed allotype were evident in the spleens of suppressed mice 4 to 6 weeks after cessation of the suppression regimen, whereas B-1 B cells of the suppressed allotype were undetectable for up to 9 months. Although serum IgM of the suppressed allotype was initially depleted in mice suppressed for either allotype, by 7 months of age, there were detectable levels of IgM of the suppressed allotype in the serum; however, the levels were significantly below that found in nonsuppressed mice. When mice were immunized with either the T-independent or T-dependent form of phosphorylcholine, those suppressed for either allotype, and consequently depleted of B-1 B cells of that allotype, did not respond with phosphorylcholine-specific IgM of the suppressed allotype. In contrast, when mice were immunized with 1-3 dextran, the Igh6a allotype-suppressed mice were able to produce dextran-specific IgM of that allotype. -
Role of Igg3 in Infectious Diseases
Review Role of IgG3 in Infectious Diseases 1 2 1 1, Timon Damelang, Stephen J. Rogerson, Stephen J. Kent, and Amy W. Chung * IgG3 comprises only a minor fraction of IgG and has remained relatively under- Highlights studied until recent years. Key physiochemical characteristics of IgG3 include IgG3 has been associated with enhanced control or protection against an elongated hinge region, greater molecular flexibility, extensive polymor- a range of intracellular bacteria, para- phisms, and additional glycosylation sites not present on other IgG subclasses. sites, and viruses. These characteristics make IgG3 a uniquely potent immunoglobulin, with the IgG3 Abs are potent mediators of potential for triggering effector functions including complement activation, effector functions, including enhanced antibody (Ab)-mediated phagocytosis, or Ab-mediated cellular cytotoxicity ADCC, opsonophagocytosis, comple- ment activation, and neutralization, (ADCC). Recent studies underscore the importance of IgG3 effector functions compared with other IgG subclasses. against a range of pathogens and have provided approaches to overcome IgG3-associated limitations, such as allotype-dependent short Ab half-life, and Future Ab-based therapeutics and vaccines should consider utilizing excessive proinflammatory activation. Understanding the molecular and func- IgG3, based on features of enhanced tional properties of IgG3 may facilitate the development of improved Ab-based functional capacity. immunotherapies and vaccines against infectious diseases. Investigating the impact of glycosyla- tion patterns and allotypes on IgG3 Human IgG3 an Understudied but Highly Potent Immunoglobulin function may expand our understand- Antibodies (Abs) play a major role in protection against infections by binding to and inactivating ing of IgG3 responses and their ther- apeutic potential. invading pathogens. -
Epitopes, Isotypes, Allotypes, Idiotypes
Epitope • Epitope or antigenic determinant- is a portion of a foreign protein, or antigen, that is capable of stimulating an immune response. • An epitope is the part of the antigen that binds to a specific antigen receptor on the surface of a B cell (BCR). • Binding between the receptor and epitope occurs only if their structures are complementary. • If they are, epitope and receptor fit together like lock and key. This binding is necessary to activate B-cell for the production of antibodies. • The antibodies produced by B cells are targeted specifically to the epitopes that bind to the cells’ antigen receptors. • Thus, the epitope also is the region of the antigen that is recognized by specific antibodies, which bind to and remove the antigen from the body. Isotype • Each antibody has only one type of (γ, or α, or μ, or ε, or δ) heavy chain and one type of (k or λ) light chain. • The structural differences in the constant region of a heavy chain or light chain determine immunoglobulin (Ig) class and sub- class, types and subtypes within a species. • These constant region determinants are called isotypic determinants or isotypes. Allotype • Based on the genetic difference among individuals. • Although all members of a species inherit the same set of isotype genes, multiple alleles exist for some of the genes. • These alleles encode minor amino acid differences, known as allotypic determinants. • Occurs in some but not all members of a species. • The sum of the individual allotypic determinants displayed by an antibody determines its allotype. Allotypic determinants Idiotype • VH and VL domains of an antibody constitute an antigen-binding site. -
Involvement of Haptens in Allergic and Non-Allergic Hypersensitivity
Polish J. of Environ. Stud. Vol. 18, No 3 (2009), 325-330 Review Involvement of Haptens in Allergic and Non-Allergic Hypersensitivity E. Kucharska1*, J. Bober2**, L. Jędrychowski3*** 1Department of Human Nutrition, Faculty of Food Sciences and Fisheries, West-Pomeranian University of Technology, Papieża Pawła VI no. 3, 71-459 Szczecin, Poland 2Department of Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72, 70-111 Szczecin, Poland 3Institute of Animal Reproduction and Food Research of the Polish Academy of Sciences in Olsztyn, Tuwima 10, 10-747 Olsztyn, Poland Received: 7 July 2008 Accepted: 11 December 2008 Abstract The environment is used as a broad umbrella term for all sources of allergens which may cause allergic hypersensitive reaction of the immune system of humans. Westernization of life leads to increased average consumption of food additives (natural and xenobiotics) – starting from over 5kg (10lbs) annually with a strong tendency to intensify. Modern technologies of food production often employ substances improving quality, texture, colour, taste, acidity or alkalinity. Haptens present in food or drugs, penetrating organism via gastrointestinal tract, may be responsible for symptoms not only in the gastrointestinal tract itself, but also in peripheral organs. Mechanisms of hapten action within human body are different – they include reactions when the immune system is involved (allergic hypersensitivity) and not involved (food intolerance also known as non-allergic hypersensitivity). Food intolerance is a more frequent phenomenon diagnosed in 20-50% of cases; food allergy affecting 6-8% children and 1-2% adults. Our work elucidates mechanisms of hypersensi- tivity responses to haptens, and characterizes major haptens applied as food additives. -
Immunostimulatory Activity of Haptenated Proteins
Immunostimulatory activity of haptenated proteins Noah W. Palm and Ruslan Medzhitov1 Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, New Haven, CT 06510 Communicated by Richard A. Flavell, Yale University School of Medicine, New Haven, CT, September 30, 2008 (received for review July 15, 2008) Antigen recognition alone is insufficient for the activation of In previous studies, we investigated the role of the TLR adaptive immune responses mediated by conventional lympho- signaling pathway in the induction of adaptive immune re- cytes. Additional signals that indicate the origin of the antigen are sponses, using mice deficient in the critical TLR signaling also required. These signals are generally provided by the innate adaptor Myeloid Differentiation primary response gene 88 immune system upon recognition of conserved microbial struc- (MyD88) (9, 10). To isolate the contribution of TLRs we used a tures by a variety of pattern recognition receptors (PRRs). The single defined TLR ligand, Lipopolysaccharide (LPS), as an Toll-like receptors (TLRs) are the best-characterized family of PRRs adjuvant, and the native proteins ovalbumin (OVA) or human and control the activation of adaptive immune responses to a serum albumin (HSA), as model antigens. incomplete Freund’s variety of immunizations and infections. However, recent studies adjuvant (IFA) and aluminum hydroxide, which contain low have questioned the role of TLRs in the induction of antibody levels of contaminating -
Major Histocompatibility Complex Class III Genes and Susceptibility to Immunoglobulin a Deficiency and Common Variable Immunodeficiency
Major histocompatibility complex class III genes and susceptibility to immunoglobulin A deficiency and common variable immunodeficiency. J E Volanakis, … , H W Schroeder Jr, M D Cooper J Clin Invest. 1992;89(6):1914-1922. https://doi.org/10.1172/JCI115797. Research Article We have proposed that significant subsets of individuals with IgA deficiency (IgA-D) and common variable immunodeficiency (CVID) may represent polar ends of a clinical spectrum reflecting a single underlying genetic defect. This proposal was supported by our finding that individuals with these immunodeficiencies have in common a high incidence of C4A gene deletions and C2 rare gene alleles. Here we present our analysis of the MHC haplotypes of 12 IgA-D and 19 CVID individuals from 21 families and of 79 of their immediate relatives. MHC haplotypes were defined by analyzing polymorphic markers for 11 genes or their products between the HLA-DQB1 and the HLA-A genes. Five of the families investigated contained more than one immunodeficient individual and all of these included both IgA-D and CVID members. Analysis of the data indicated that a small number of MHC haplotypes were shared by the majority of immunodeficient individuals. At least one of two of these haplotypes was present in 24 of the 31 (77%) immunodeficient individuals. No differences in the distribution of these haplotypes were observed between IgA-D and CVID individuals. Detailed analysis of these haplotypes suggests that a susceptibility gene or genes for both immunodeficiencies are located within the class III region of the MHC, possibly between the C4B and C2 genes. Find the latest version: https://jci.me/115797/pdf Major Histocompatibility Complex Class Ill Genes and Susceptibility to Immunoglobulin A Deficiency and Common Variable Immunodeficiency John E. -
Monoclonal Antibodies Specific for Mercuric Ions (Hybridomas/Metals) DWANE E
Proc. Natl. Acad. Sci. USA Vol. 89, pp. 4104-4108, May 1992 Immunology Monoclonal antibodies specific for mercuric ions (hybridomas/metals) DWANE E. WYLIE*tt, Di Lut, LARRY D. CARLSON*, RANDY CARLSONt, K. FUNDA BABACAN§, SHELDON M. SCHUSTERt¶, AND FRED W. WAGNER*II tSchool of Biological Sciences, University of Nebraska, Lincoln, NE 68588; tBioNebraska, Inc., 3940 Cornhusker Highway, Lincoln, NE 68504; §Department of Microbiology, University of Marmara, Istanbul, Turkey; IDepartment of Biochemistry and Molecular Biology, J. Hillis Miller Health Center, University of Florida, Gainesville, FL 32610; and I'Department of Biochemistry, University of Nebraska, Lincoln, NE 68583 Communicated by Clarence A. Ryan, February 6, 1992 (received for review August 8, 1991) ABSTRACT Monoclonal antibodies (mAbs) that react These observations indicate that metals can at least influ- with soluble mercuric ions have been produced by i 'ection of ence antibody specificity and, rarely, in immunopathological BALB/c mice with a hapten-carrier complex designed to conditions, can serve as haptens toward which an antibody maximize exposure of the metal to the immune system. Three response can be directed. This report describes the produc- hybridomas producing antibodies that reacted with bovine tion of monoclonal antibodies (mAbs) specific for soluble serum albumin (BSA)-glutathione-HgCI, but not with BSA- mercuric ions by immunization of BALB/c mice with a glutathione, were isolated from the spleen of a mouse given complex consisting of mercuric chloride-glutathione- multiple iqjections with glutathione-HgCl conjugated to key- keyhole limpet hemocyanin (KLH). hole limpet hemocyanin. Stable subclones were established from two of these antibodies, designated mAb 4A10 and mAb MATERIALS AND METHODS IF10. -
Immunoglobulin Allotypes and Immune Response to Meningococcal Group B Polysaccharide
Immunoglobulin allotypes and immune response to meningococcal group B polysaccharide. J P Pandey, … , H H Fudenberg, C B Loadholt J Clin Invest. 1981;68(5):1378-1380. https://doi.org/10.1172/JCI110387. Research Article Serum samples were collected from 120 healthy adult volunteers (105 Caucasians and 15 Negros) before and after immunization with meningococcal polysaccharide (MPS) group B vaccine. Antibodies to MPS group B were measured and sera were typed for several Gm and Km(1) allotypes. A significant association was found between the Km(1) allotype and immune response to MPS group B in Caucasians. Find the latest version: https://jci.me/110387/pdf Immunoglobulin Allotypes and Immune Response to Meningococcal Group B Polysaccharide JANARDAN P. PANDEY, WENDELL D. ZOLLINGER, H. HUGH FUDENBERG, and C. BOYD LOADHOLT, Department of Basic and Clinical Immunology and Microbiology, Department of Biometry, Medical University of South Carolina, Charleston, South Carolina 29425; Department of Bacterial Diseases, Walter Reed Army Institute of Research, Washington, D. C. 20012 A B S T R A C T Serum samples were collected from METHODS 120 healthy adult volunteers (105 Caucasians and 15 Subjects and vaccines. A total of 120 healthy adult male Negros) before and after immunization with meningo- volunteers (105 Caucasians and 15 Negroes), 18-21 yr of age, coccal polysaccharide (MPS) group B vaccine. Anti- were vaccinated with meningococcal group B vaccine (120 bodies to MPS group B were measured and sera were ,ig in 0.5 ml of saline), either lot BP2-WZ-2 or lot BP2-4. Gm A The two lots of vaccine are of similar composition and anti- typed for several and Km(l) allotypes. -
I M M U N O L O G Y
I M M U N O L O G Y B T Immunology 2 Career Avenues GATE Coaching by IITians Table of Contents Introduction to Immune System ....................................................................................................... 4 Primary and Secondary Lymphoid Organs ...................................................................................... 12 Antigen ..................................................................... 26 Cells of Immune System .................................................................................................................. 33 Major Histocompatibility Complex ................................................................................................. 48 Antigen Processing and Presentation ............................................................................................. 51 Immunoglobulins ............................................................................................................................ 53 Origin of Antibody Diversity ........................................................................................................... 64 Polyclonal and Monolclonal Antibodies .......................................................................................... 66 Complement ............................................................. 70 Antigen-Antibody Reaction ............................................................................................................. 77 Regulation of Immune Response ................................................................................................... -
I M M U N O L O G Y Core Notes
II MM MM UU NN OO LL OO GG YY CCOORREE NNOOTTEESS MEDICAL IMMUNOLOGY 544 FALL 2011 Dr. George A. Gutman SCHOOL OF MEDICINE UNIVERSITY OF CALIFORNIA, IRVINE (Copyright) 2011 Regents of the University of California TABLE OF CONTENTS CHAPTER 1 INTRODUCTION...................................................................................... 3 CHAPTER 2 ANTIGEN/ANTIBODY INTERACTIONS ..............................................9 CHAPTER 3 ANTIBODY STRUCTURE I..................................................................17 CHAPTER 4 ANTIBODY STRUCTURE II.................................................................23 CHAPTER 5 COMPLEMENT...................................................................................... 33 CHAPTER 6 ANTIBODY GENETICS, ISOTYPES, ALLOTYPES, IDIOTYPES.....45 CHAPTER 7 CELLULAR BASIS OF ANTIBODY DIVERSITY: CLONAL SELECTION..................................................................53 CHAPTER 8 GENETIC BASIS OF ANTIBODY DIVERSITY...................................61 CHAPTER 9 IMMUNOGLOBULIN BIOSYNTHESIS ...............................................69 CHAPTER 10 BLOOD GROUPS: ABO AND Rh .........................................................77 CHAPTER 11 CELL-MEDIATED IMMUNITY AND MHC ........................................83 CHAPTER 12 CELL INTERACTIONS IN CELL MEDIATED IMMUNITY ..............91 CHAPTER 13 T-CELL/B-CELL COOPERATION IN HUMORAL IMMUNITY......105 CHAPTER 14 CELL SURFACE MARKERS OF T-CELLS, B-CELLS AND MACROPHAGES...............................................................111 -
The Fate of a Hapten
www.nature.com/scientificreports OPEN The Fate of a Hapten - From the Skin to Modifcation of Macrophage Migration Inhibitory Factor (MIF) in Received: 14 September 2017 Accepted: 31 January 2018 Lymph Nodes Published: xx xx xxxx Isabella Karlsson 1, Kristin Samuelsson2, Carl Simonsson2, Anna-Lena Stenfeldt2, Ulrika Nilsson1, Leopold L. Ilag1, Charlotte Jonsson2 & Ann-Therese Karlberg2 Skin (contact) allergy, the most prevalent form of immunotoxicity in humans, is caused by low molecular weight chemicals (haptens) that penetrate stratum corneum and modify endogenous proteins. The fate of haptens after cutaneous absorption, especially what protein(s) they react with, is largely unknown. In this study the fuorescent hapten tetramethylrhodamine isothiocyanate (TRITC) was used to identify hapten-protein conjugates in the local lymph nodes after topical application, as they play a key role in activation of the adaptive immune system. TRITC interacted with dendritic cells but also with T and B cells in the lymph nodes as shown by fow cytometry. Identifcation of the most abundant TRITC-modifed protein in lymph nodes by tandem mass spectrometry revealed TRITC-modifcation of the N-terminal proline of macrophage migration inhibitory factor (MIF) – an evolutionary well-conserved protein involved in cell-mediated immunity and infammation. This is the frst time a hapten-modifed protein has been identifed in lymph nodes after topical administration of the hapten. Most haptens are electrophiles and can therefore modify the N-terminal proline of MIF, which has an unusually reactive amino group under physiological conditions; thus, modifcation of MIF by haptens may have an immunomodulating role in contact allergy as well as in other immunotoxicity reactions. -
Monovalent and Divalent Haptens with Dual Specificity Monoclonal Antibody Conjugates: Enhanced Divalent Hapten Affinity for Cell Bound Antibody Conjugate
In Vitro and In Vivo Targeting of Radiolabeled Monovalent and Divalent Haptens with Dual Specificity Monoclonal Antibody Conjugates: Enhanced Divalent Hapten Affinity for Cell Bound Antibody Conjugate Jean-Marc Le Doussal, Marie Martin, Emmanuel Gautherot, Michel Delaage, and Jacques Barbet Immunotech S.A., Campus de Luminy, Marseilles, France A method of pretargeted immunolocalizationof a mouse cell subset, using dual specificity monoclonalantibody conjugates and labeled divalent haptens, is described. Conjugates were prepared by coupling F(ab')@fragments of an antibody specificfor the allelicmouse B cell antigen Lyb8.2, to Fab' fragments of an anti-2,4-dinitrophenyl antibody. Divalent and monovalent haptens were obtained by coupling dinitrophenylto peptides or to diethylene tnamine-pentaacetic acid. In vitro, divalent haptens bind with higher affinityto mouse spleen lymphocyte-bound than to excess soluble conjugate (affinityenhancement). Invivo, localizationof 1251or 111ln-labeleddivalent haptens in mouse spleen is much higher than that ofthemonovalentanalogs.Thus,usingdivalenthaptens,a newkindofspecificitytotarget cells was achieved, suggesting that affinity enhancement may improve target to background ratios in radioimmunoscintigraphy. J Nucl Med30: 1358—1366,1989 ecently, the use of low molecular weight tracers, affinity of the DSC towards the hapten. Indeed, when such as indium chelates, associated with dual specificity the affinity is too strong, the tracer is effectively trapped antibody conjugates (DSC), combining antibodies (or by excess circulating DSC: its specific localization and fragments) to the target cells with high affinity antibod its clearance are impaired (3). Ifthis affinity is too low, ies (or fragments) to the indium chelate (dissociation no specificlocalizationwould be obtained.To take constant in the nM range), has been proposed for in advantage of the theoretical potential of the method, vivo radioimmunolocalization and radioimmunother excess DSC should be removed from the circulation apy ( 1).