Histocompatibility Antigens: Structure and Function PDF
Preview Histocompatibility Antigens: Structure and Function
Receptors and Recognition General Editors: P. Cuatrecasas and M.F. Greaves About the series Cellular Recognition - the process by which cells interact with, and respond to, molecular signals in their environment - plays a crucial role in vitually all important biological functions. These encompass fertilization, infectious interactions, embryonic development, the activity of the nervous system, the regulation of growth and metabolism by hormones and the immune response to foreign antigens. Although our knowledge of these systems has grown rapidly in recent years, it is clear that a full understanding of cellular recognition phenomena will require an integrated and multidisciplinary approach. This series aims to expedite such an understanding by bringing together accounts by leading researchers of all biochemical, cellular and evolutionary aspects of recognition systems. This series will contain volumes of two types. First, there will be volumes containing about five reviews from different areas of the general subject written at a level suitable for all biologically oriented scientists (Receptors and Recognition, series A). Secondly, there will be more specialized volumes (Receptors and Recognition, series B), each of which will be devoted to just one particularly important area. Advisory Editorial Soard K.F. Austen, Harvard Medical School, Boston, U.S.A. E.A. Boyse, Memorial Sloan-Kettering Cancer Center, New York, U.S.A. M.1. Crumpton, Imperial Cancer Research Fund Laboratories, London, U.K. M. Edidin, The Johns Hopkins University, Baltimore, U.S.A. N.B. Gilula, The Rockefeller University, New York, U.S.A. L.L. Iversen, MRC Neurochemical Pharmacology Unit, Cambridge, U.K. J. Lilien, The University of Wisconsin, U.S.A. V.T. Marchesi, Yale University, New Haven, U.S.A. S. Ohno, City of Hope National Medical Center, California, U.S.A. L. Philipson, University of Uppsala, Sweden. M. Raft, University College London, U.K. M. Rodbell, National Institutes of Health, Bethesda, U.S.A. M. Sela, The Weizmann Institute of Science, Israel. S.H. Snyder, The Johns Hopkins University, Baltimore, U.S.A. D.F.H. Wallach, Tufts University School of Medicine, Boston, U.S.A. L. Wolpert, The Middlesex Hospital Medical School, London, U.K. Receptors and Recognition Series A Published Volume 1 (1976) M.F. Greaves (London), Cell Surface Receptors: A Biological Perspective F. Macfarlane Burnet (Melbourne), The Evolution of Receptors and Recognition in the Immune System K. Resch (Heidelberg), Membrane Associated Events in Lymphocyte Activation K.N. Brown (London), Specificity in Host-Parasite Interaction Volume 2 (1976) D. Givol (Jerusalem), A Structural Basis for Molecular Recognition: The Antibody Case B.D. Gomperts (London), Calcium and Cell Activation M.A.B. de Sousa (New York), Cell Traffic D. Lewis (London), Incompatibility in Flowering Plants A. Levitski (Jerusalem), Catecholamine Receptors Volume 3 (1977) J. Lindstrom (Salk, California), Antibodies to Receptors for Acetylcholine and other Hormones M. Crandall (Kentucky), Mating-Type Interaction in Micro-organisms H. Furthmayr (New Haven), Erythrocyte Membrane Proteins M. Silverman (Toronto), Specificity of Membrane Transport Volume 4 (1977) M. Sonenberg and A.S. Schneider (New York), Hormone Action at the Plasma Membrane: Biophysical Approaches H. Metzger (NIH, Bethesda), The Cellular Receptor for IgE T.P. Stossel (Boston), Endocytosis A. Meager (Warwick) and R.C. Hughes (London), Virus Receptors M.E. Eldefrawi and A.T. Eldefrawi (Baltimore), Acetylcholine Receptors Volume 5 (1978) P.A. Lehmann (Mexico), Stereoselective Molecular Recognition in Biology A.G. Lee (Southampton, U.K.), Fluorescence and NMR Studies of Membranes L.D. Kohn (NIH, Bethesda), Relationships in the Structure and Function of Receptors for Glycoprotein Hormones, Bacterial Toxins and Interferon Volume 6 (1978) J.N. Fain (Providence, Rhode Island), Cyclic Nucleotides G.D. Eytan (Haifa) and B.I. Kanner (Jerusalem), Reconstitution of Biological Membranes P.J. O'Brien (NIH, Bethesda), Rhodopsin: A Light-sensitive Membrane Glycoprotein Index to Series A. Volumes 1-6 Series B Published The Specificity and Action of Animal Bacterial and Plant Toxins (BI) edited by P. Cuatrecasas (Burroughs Wellcome, North Carolina) Intercellular Junctions and Synapses (B2) edited by J. Feldman (London), N.B. Gilula (Rockefeller University, New York) and J.D. Pitts (University of Glasgow) Microbial Interactions (B3) edited by J.L. Reissig (Long Island University, New York) Specificity of Embryological Interactions (B4) edited by D.R. Garrod (University of Southampton) Taxis and Behavior (BS) edited by G.L. Hazelbauer (University of Uppsala) Bacterial Adherence (B6) edited by E.H. Beachey (Veteran's Administration Hospital and University of Tennessee, Memphis, Tennessee) Virus Receptors Part 1 Bacterial Viruses (B7) edited by L.L. Randall and L. Philipson (University of Uppsala) Virus Receptors Part 2 Animal Viruses (BS) edited by K. Lonberg-Holm (Du Pont, Delaware) and L. Philipson (University of Uppsala) Neurotransmitter Receptors Part 1 Amino Acids, Peptides and Benzodiazepines (B9) edited by S.J. Enna (University of Texas at Houston) and H.I. Yamamura (University of Arizona) Neurotransmitter Receptors Part 2 Biogenic Amines (BlO) edited by H.I. Yamamura (University of Arizona) and S.I. Enna (University of Texas at Houston) Membrane Receptors: Methods for Purification and Characterization (Bll) edited by S. Jacobs and P. Cuatrecasas (Burroughs Wellcome, North Carolina) Purinergic Receptors (BI2) edited by G. Burnstock (University College, London) Receptor Regulation (B13) edited by R.I. Lefkowitz (Duke University Medical Center, North Carolina) Receptors and Recognition Series B Volume 14 Histocompatibility Antigens Structure and Function Edited by P.Parham Stanford University School of Medicine California and J. Strominger Harvard University Massachussetts LONDON NEW YORK CHAPMAN AND HALL First published 1982 by Chapman and Hall Ltd, 11 New Fetter Lane, London EC4P 4EE Published in the USA by Chapman and Hall 733 Third Avenue, New York, NY 10017 © 1982 Chapman and Hall Softcover reprint of the hardcover 1st edition 1982 Typeset by Preface Ltd, Salisbury, Wilts. and printed in Great Britain at the University Printing House, Cambridge ISBN-13:978-94-009-5896-8 All rights reserved. No part of this book may be reprinted, or reproduced or utilized in any form or by any electronic, mechanical or other means, now known or hereafter invented, including photocopying and recording, or in any information storage and retrieval system, without permission in writing from the publisher British Library Cataloguing in Publication Data Histocompatibility antigens: structure and function. -(Receptors and recognition. Series B; v. 14) 1. Antigens and antibodies I. Parham, P. II. Strominger, J. III. Series 574.2'92 QR186.5 ISBN-13:978-94-009-5896-8 e-ISBN-13:978-94-009-5894-4 DOl: 10.1007/978-94-009-5894-4 Contents Contributors page Vlll Preface ix 1 The Major Histocompatibility Complex: Analysis at the Protein and DNA Levels 1 Harry. T. Orr 2 The Interaction of MHC Antigens with the Plasma Membrane and the Other Cellular Components 53 Matthew F. Mescher 3 Involvement of Self in the Interactions of Lymphocytes and Target Cells: Some Speculations on the Nature of MHC Restriction 85 Judith A. Owen, Neil Greenspan and Peter C. Doherty 4 Antigen Recognition and Cytotoxic T Lymphocytes: An Overview with Emphasis on Properties of Target Cells 119 Mark S. Pasternack and Herman N. Eisen 5 Immune Response Genes and Ia Antigens. The Relationship Between Them and Their Role in Lymphocyte Interactions 159 Dan L. Longo and William E. Paul 6 MHC·Linked Complement Components 187 Donald C. Shreffler 7 Evolution and Function of the Major Histocompatibility Complex 221 Jan Klein Index 241 Contributors Peter C. Doherty, Wistar Institute, Spruce Street, Philadelphia, Pennsylvania 19129, U.S.A. Herman N. Eisen, Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, U.S.A. Neil Greenspan, Wistar Institute, Spruce Street, Philadelphia, Pennsylvania 19129, U.S.A. Jan Klein, Abteilung Immungenetik, Max-Plank-Institute fur Biologie Tiibingen, 7400 Tiibingen, Federal Republic of Germany. Dan L. Longo, Medicine Branch, National Cancer Institute and the Labora tory of Immunology, Bethesda, Maryland 20205, U.S.A. Matthew F. Mescher, Department of Pathology, Harvard Medical School, BOSjQIl)M(lssachu~setts 02115, U.S.A. Harry T. Orr, Immunobiology Research Center, Department of Laboratory Medicine and Pathology, Medical School, Box 724, Mayo Memorial Build ing, 420 Delaware Street SE, Minneapolis, Minnesota 55455, U.S.A. (Formerly at the Department of Biochemistry and Molecular Biology, Har vard University, Cambridge, Massachussetts.) Judith A. Owen, Wistar Institute, Spruce Street, Philadelphia, Pennsylvania 19129, U.S.A. Mark S. Pasternack, Center for Cancer Research, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, U.S.A. William E. Paul, Medicine Branch, National Cancer Institute and the Laboratory of Immupology, Bethesda, Maryland 20205, U.S.A. Donald C. Shremer, Department of Genetics, Washington University School of Medicine, St. Louis, Missouri 63130, U.S.A. Preface The Major Histocompatibility Complex (MHC) was discovered as a con sequence of the chronic problem encountered by cancer biologists in the early years of this century: the failure to maintain tumor lines by serial passage in outbred mice. A number of observations pointed to genetic similarity being a prerequisite for successful transplantation and they were incorporated into a genetic theory of transplantation by C.C. Little. This prompted scientists like Little to initiate breeding experiments designed to test his hypothesis and produce genetically identical mice which would permit the growth of trans planted tumors. Most inbred strains of mice commonly used in immunology derive from those efforts. Transplantation of normal tissues obeyed the same rules found for malignant tissues and rejection was shown to be an immunological phenomenon. G.D. Snell showed that a single genetic locus determined rapid rejection of skin grafts. This was initially called the Major Histocompatibility Locus but was subsequently shown to include many functionally related genes and renamed the Major Histocompatibility Complex (MHC). In mouse this is the H-2 complex and man the HLA complex. During this same period P.A. Gorer, taking a different approach, was identifying blood group alloantigens, postulated to be the agents responsible for tissue rejection. This turned out to be true and he was able to show that transplant rejection was accompanied by the production of alloantibodies against alloantigens of the graft not found on host tissues. They became known as transplantation antigens. The serology of Gorer and histogenetics of Snell were unified by the discovery that the trans plantation antigens were the products of genes in the MHC. Subsequently, in the period 1950-1970 the H-2 complex of mouse and its extremely polymorphic products, the H-2 antigens, were extensively analysed by immunogenetic methods. This has been reviewed by Klein (1975), Snell et al. (1976) and Festenstein and Demant (1978). Analagou,s studies in man, initiated by J. Dausset, R. Payne and J.J. van Rood in the late 1950s revealed a similar system of genetically inherited alloantigens now known as HLA antigens and coded for by the HLA locus. In general these studies were of little interest to biologists because of the artifactual nature of the defining phenomenon - transplantation. Neither were surgeons greatly aroused, as the increased understanding of MHC antigens provided little help in preventing or manipulating graft rejection. During this same period cellular immunology had undergone a renaissance and was flourishing in the schools established by M. Burnet, P. Medawar and x Preface J. Gowans. Mice were the common experimental system and the inbred strains were crucial to the development of adoptive transfer systems now commonly used to dissect cellular reactions in immune responses. The clonality of lymphocytes was appreciated and they were divided into functional sub-sets responsible for antibody synthesis (B cells) and for a con stellation of activities historically associated with cellular immunity (T cells). In the process of these investigations, it was discovered that MHC genes imposed certain restrictions on functional interactions between lymphocytes and various other cells in the immune response. This MHC restriction is a consequence of the mechanism by which T cells recognize foreign antigens. Unlike B cells, which have immunoglobulin receptor molecules that can inde pendently bind antigens, T cells are only functionally responsive to antigen when it can be recognized in association with the appropriate MHC antigen. What the appropriate MHC antigen is depends on two factors: (1) the functional sub-set to which the T cell belongs and (2) the MHC antigens encountered by the T cell during its differentiation. The existence of this seemingly baroque system for recognizing foreign antigens in the context of self antigens is probably a reflection of the evolutionary development of receptor molecules rather than subtlety of design. However bizarre, these phenomena do provide a genuine biological function for the MHC antigens which also accounts for their covert existence as transplantation antigens. It now seems likely that MHC antigens are a family of molecules with an importance for the immune system equivalent to that of the immunoglobulins. This notion was recently endorsed by the award of the Nobel Prize for Medicine and Physiology, 1980, to Snell, Dausset and Benacerraf. As pointed out by Medawar (1981) in his review of this award, 'The discovery and characterization of H-2 and HLA provides an exemplary case history in rebuttal of the notion that scientific discovery can be pre meditated'. This observation is particularly pertinent to the molecular and biochemical analysis of MHC antigens. Although MHC antigens could only be assayed by virtue of their polymorphic antigenic determinants this did not deter biochemists from identifying and characterizing the molecules responsible for the serological activity. The acquisition of information in this field has involved persistent and heroic efforts with few of the elegant short cuts to understanding that appear so routinely in modern molecular biology. For example a formidable statistic can be found in an early paper by S. Nathenson describing the purification of H-2 antigens: 'the preparation of H-2 antigens was by a pro cedure using 4000 frozen spleens from either C57 B1/6 or DBA/ mice'. The reward of such efforts is that we now have a remarkable, though very incom plete, knowledge of these molecules and they provide some of the best under stood examples of a eukaryotic membrane glycoprotein. In addition, the amino acid sequences of some MHC gene products show intriguing homology Preface Xl with immunoglobulin chains, the knowledge of which may help further study of the function of these molecules. To describe the history, serology and genetics of the MHC is hardly it well-trodden path, more like the M1 or the New Jersey Turnpike. In this collection of reviews we deliberately tried to downplay any detailed description of these topics and refer the reader to the following texts: Klein (1975), Snell et al. (1976), Gotze (1977), Festenstein and Demant (1978), and Svejgaard et al. (1979). Our intent was to provide a current assessment of our knowledge of MHC antigens and how they fit into the greater picture of the immune system. The articles require some knowledge of immunology and the MHC and a background acquaintance with biochemistry and genetics. They are primarily aimed at the graduate level or higher but will also be of use to the interested undergraudate or medical student. The exciting puzzles and unanswered questions confronted by those working on or with MHC products focus on the exact molecular processes by which MHC restriction of T cell recognition is created in development and then used in immune responses. The approaches that are being used are indicative of the progressive blurring of disciplines that is seen in many areas of biological research. Cellular immunology, membrane biochemistry, molecular biology, monoclonal antibody serology and population genetics all contribute to current research on MHC products. It seems clear that a functionally defined, biochemically mysterious entity called the T cell receptor( s) is (are) involved in the recognition of foreign antigen and MHC antigens. This provided our starting point for compiling a book on MHC gene products to be included in Receptors and Recognition Series B. The outcome is to be found in the following seven chapters. REFERENCES Festenstein, H. and Demant, P. (1978), HLA and H-2: Basic Immunogenetics, Biology and Clinical Relevance; Current Topics in Immunology Series. Edward Arnold Press, London. G6tze, D. (ed) (1977), The Major Histocompatibility System in Man and Animals. Springer-Verlag, Berlin. Klein, J. (1975) Biology of the Mouse Histocompatibility-2 Complex. Springer-Verlag, New York. Medawar, P. (1981), Nature, 289,345. Shimada, A. and Nathenson, S.G. (1969), Biochemistry, 8: 4048-4062. Snell, G.D., Dausset, J. and Nathenson, S. (1976), Histocompatibility. Academic Press, New York. Svejgaard, A., Hauge, M., Jersild, c., Platz, P., Ryder, L.P., Staub Nielsen, L. and Thomsen, M. (1979), The HLA system, In: Monographs in Human Genetics 7 (L. Beckman, U. Hauge and M. Hauge, eds), Karger, Basel.
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