Immunodominance – The Choice of the Immune System

Jeffrey A. Frelinger received his Ph.D. in immunology at the California Institute of Technology, Pasadena in 1973 and worked as a post-doc at the University of Michigan Medical School, Ann Arbor. Since 1988 he is professor and chair at the Department of Microbiology and Immunology and Associate Director for Research at the Center for Infectious Disease at the University of North Carolina, School of Medicine, Chapel Hill, USA. His major research interests are immunogenetics, molecular immunology and cellular immunology.

Preface.List of Contributors.Color Plates.I Mechanics of Antigen Processing.1 Class I MHC Antigen Processing (Peter J. Miller and Edward J. Collins).1.1 Introduction.1.2 Properties of MHC.1.3 Properties of Peptides.1.4 Cytosolic Processing.1.5 Peptide Transport.1.6 Class I MHC Maturation and Peptide Loading.1.7 Immunodominance and Class I MHC Peptide Processing.2 The Mechanics of Class II Processing: Establishment of a Peptide Class II Hierarchy (James R. Drake and Andrea J. Sant).2.1 General Overview.2.2 Phase I: MHC Class II Biosynthesis and Delivery to Peptide-loading Compartments.2.3 Phase II: Antigen Internalization and Processing.2.4 Phase III: Formation and Expression of Antigenic Peptide by MHC Class II Molecules.2.5 Conclusions.Acknowledgments.3 The Phenomenon of Immunodomination: Speculations on the Nature of Immunodominance (Alessandro Sette and Roshni Sundaram).3.1 Introduction.3.2 MHC Binding, Cellular Processing, and T-Cell Repertoire are Major Determinants of Immunodominance.3.3 Previous Systematic Analysis of Immunodominance by Our Group.3.4 Cellular and Molecular Events in Immunodomination.3.5 Speculations on the Mechanism of Immunodomination.3.6 Significance of Studying Immunodominance for Vaccine Development.3.7 Conclusions.II Proteosome Specificityand Immuno-Proteosomes.4 Endogenous Antigen Processing (Jonathan W. Yewdell).4.1 Unbottling the Genie.4.2 DRiPs to the Rescue.4.3 The Ubiquitin-Proteasome Pathway.4.4 Pressing TDH Questions.4.5 What Does This Have to Do With Immunodominance?III Effect of the T Cell Repertoire on Dominance.5 Regulation of EarlyT-C ell Development in the Thymus (Thomas M. Schmitt and Juan Carlos Zuniga-Pflucker).5.1 Introduction.5.2 T-Cell Development in the Thymus.5.3 In Vitro T-cell Development.5.4 Concluding Remarks.6 CD8 T-cell Immunodominance, Repertoire, and Memory (Dalia E. Gaddis, Michael J. Fuller, and Allan J. Zajac).6.1 Introduction.6.2 CD8 T-Cell Responses and Memory.6.3 Analyzing the Memory Repertoire.6.4 Immunodominance.6.5 Epitope-dependent Skewing of the Repertoire During Primary, Memory, and Recall Responses.6.6 Heterologous Infections and Immunodominance.6.7 Chronic Infections and T-cell Heterogeneity.6.8 Repertoire Limitation and Immunodominance.6.9 Impact of Epitope Variation.6.10 Concluding Remarks.IV Effects of Pathogens on the Immune Response.7 Listeria monocytogenes Infection and the CD8+ T-Cell Hierarchy (Brandon B. Porter and John T. Harty).7.1 Introduction.7.2 Innate Immune Response to LM.7.3 Adaptive Immune Response to LM and Ag Presentation.7.4 Secreted Versus Non-secreted Ag.7.5 The Hierarchy of the CD8+ T-cell Responses to LM Epitopes.7.6 IFN-c and the CD8+ T-cell Hierarchy.7.7 Timing of Ag Presentation and the CD8+ T-cell response.7.8 Conclusions.Acknowledgments.8 Immunodominance in Tuberculosis (David M. Lewinsohn and JoAnne L. Flynn).8.1 Immune Responses to Mycobacterium tuberculosis.8.2 BC ells.8.3 CD4 T Cells.8.4 CD8 T Cells.8.5 Antigen Processing and Presentation of Mtb Antigens.8.6 How Does Infection with Mtb Differ from Other Acute or Chronic Infections?8.7 Immunodominance in the CD4 T-cell Response.8.8 Immunodominance in the CD8 T-cell Response.8.9 Non-classically Restricted T Cells in TB.8.10 Conclusions and Implications for Future Research.Acknowledgments.9 T-Cell Specificity and Respiratory Virus Infections (Sherry R. Crowe and David L. Woodland).9.1 Introduction.9.2 Primary Immune Responses to Respiratory Virus Infections.9.3 Specificity of the Primary Immune Response.9.4 T-Cell Memory to Respiratory Virus Infections.9.5 The Specificity of Memory T Cells.9.6 Recall Responses to Secondary Infections.9.7 Immunodominance Patterns in Recall Responses.9.8 Modification of Immunodominance Hierarchies by Vaccination.9.9 Conclusions.Acknowledgments.10 Effects of Pathogens on the Immune Response: HIV (Masafumi Takiguchi).10.1 Introduction.10.2 Identification of HIV-1 CTL Epitopes.10.3 Immunodominant HIV-1 Epitopes Presented by HLA Alleles Associated With Slow Progression to AIDS and Their Escape Mutants.10.4 Immunodominant HIV-1 Epitopes Presented by HLA Alleles Associated With Rapid Progression to AIDS.10.5 Immunodominant HIV-1 Epitopes Presented by Other HLA Alleles.10.6 Escape Mutations and Viral Fitness.10.7 Effect of Nef-mediated HLA Class I Downregulation on Recognition of HIV-1-infected CD4+ T Cells by HIV-1-specific CD8+ T Cells.10.8 Skewed Maturation of HIV-1-specific CD8+ T Cells.11 The Effects of Pathogens on the Immune System: Viral Hepatitis (Mala Maini and Antonio Bertoletti).11.1 Introduction.11.2 The Viruses and the Disease.11.3 Importance of CD4 and CD8 T Cells in HBV and HCV Control.11.4 Limitations of Existing Data.11.5 Hierarchy of T-cell Responses During HBV Infection: Helper CD4 T-cell Response.11.6 Hierarchy of T-cell Responses During HBV Infection: Cytotoxic T-cell Response.11.7 Hierarchy of HCV Proteins.11.8 Hierarchy of HCV Epitopes.11.9 Immunodominance and Liver Pathology.11.10 Concluding Remarks.12 Immunodominance in the T-Cell Response to Herpesviruses (Michael W. Munks and Ann B. Hill).12.1 Introduction.12.2 General Considerations.12.3 Immunodominance in the CD8 T-Cell Response to the Three Classes of Herpesvirus.12.4 Concluding Remarks.Index.