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Introduction
Genotypic and Phenotypic Variation of HIV-1: Impact on AIDS Pathogenesis and Vaccination 1
Origin of Retroviruses 1
Phylogeny of the Lentiviral Group 3
Genetic Variability of HIV-1 5
Mechanism of Variation 5
Variation among HIV Isolates and within an Isolate 6
Rate of Fixation of Mutations 8
Phenotypic Variability of HIV-1 9
Biological Variation 9
Antigenic Variation 9
Role of the V3 Domain in HIV Infection 10
Structure of the V3 Domain 10
Principal Neutralization Domain 10
Determinant of Biological Phenotype 12
Impact of Variation of the Third Variable gp120 Region during Natural HIV-1 Infection 13
The Acute Phase of HIV-1 Infection 13
The Asymptomatic Phase 14
The Symptomatic Phase 16
Implication of Viral Diversity for Vaccine Development 18
B Cell Antigenic Site Mapping of HIV-1 Glycoproteins 34
Amino Acid Sequence Variability of HIV-1 gp120/gp41 38
Mapping of B Cell Epitopes on gp120/gp41 Using Peptides 38
gp120/gp41 B Cell Epitope Mapping Using Antipeptide Antisera 41
Synthetic Peptides as Diagnostic Reagents to Detect and Subtype Anti-HIV-1 Antibodies 42
Site-Directed Serology for Detection of HIV Infections Using Synthetic Peptides Encompassing the 605-611 Disulfide Loop of gp41 42
Synthetic Peptides as Site-Specific Reagents for Subtyping of Anti-HIV-1 Antibodies 44
Synthetic Peptides as Potential Components of Anti-HIV-1 Vaccines 45
Discontinuous Virus-Neutralizing Epitopes 47
Molecular Mimicry of gp120/gp41 B Cell Epitopes 49
Antigenic and Immunogenic Sites of HIV-2 Glycoproteins 61
Epidemiological Features and Natural History of HIV-2 Infection 62
Genomic Organization and Immunological Relatedness of HIV-1 and HIV-2 62
Animal Models for HIV Vaccine Studies 63
Antibody-Binding Antigenic Sites in the HIV-2 Glycoproteins 65
Strain- and Type-Cross-Reactive Neutralization of HIV-2 Antibody Positive Sera 67
Target Regions for Neutralizing Antibodies in the HIV-2 Glycoproteins 68
SIV Neutralization Epitopes 78
Some Structural Characteristics of the SIV Envelope 79
Neutralization Domain of the SIV Envelope 83
Epitopes of HIV-1 Glycoproteins Recognized by the Human Immune System 91
Epitopes on gp120 91
Epitopes on gp41 100
Human Antibodies to HIV-1 by Recombinant DNA Methods 112
Phage Display of Antibody Combinatorial Libraries and Selection of Specific Fab Fragments 114
Application of the Combinatorial Library Approach to the Generation of Antibodies to HIV-1 116
Neutralization of HIV-1 by Recombinant Fabs 119
Genetic Manipulation of Antibodies 120
Gene Rescue from Antibody-Producing Cell Lines 122
Alternatives to Seropositive Humans as Sources of Antibody Libraries 122
CD4+ T Cell Epitopes in HIV-1 Proteins 127
General Aspects of the CD4+ T Cell Response to HIV-1 127
The Importance of Defining CD4+ T Cell Epitopes 128
The CD4+ T Cell Response to HIV-1 in Natural Infection 129
Role of the Presenting MHC Molecule 131
Approaches to Identifying CD4+ T Cell Epitopes 133
Methods for Predicting T Cell Epitopes 134
Clonal Analysis of Human CD4+ T Cell Epitopes 135
Analysis of Peptide-Specific T Cell Responses in Infected Individuals 140
Delineation of T Cell Epitopes in Animal Models 143
Delineation of Epitopes by Sequence Analysis of Peptides Eluted from MHC Molecules 143
How Does the HIV Escape Cytotoxic T Cell Immunity? 150
Immunity to Viruses 151
Cytotoxicity T Cell Recognition of Viruses 153
Antigen Processing and HLA Class I Binding 154
Cytotoxic T Cells Specific for HIV 155
Genetic Variation in the Cytotoxic Epitopes of HIV gag 157
Subject Index 165