Histocompatibility Antigens: Structure and Function

249 Pages·1982·4.916 MB·English

by  Harry T. Orr (auth.), P. Parham, J. Strominger (eds.)

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.