MHC Molecules: Expression, Assembly and Function

Robert G. Urban, Roman M. Chicz (Autoren)

Buch | Softcover

1997 | Softcover reprint of the original 1st ed. 1996
Springer-Verlag New York Inc.
978-1-4684-6464-1 (ISBN)

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3 nant expression systems have been used to make MHC molecules con taining a single peptide of interest. To date, fifteen single peptide class I structures (incorporating three different HLA and two different H-2 allotypes/isotypes) and four additional class II structures (two single peptide complexes and two superantigen complexes) have been reported. These advances have enabled us to study the atomic detail of antigen presentation and the general mechanisms behind peptide binding, and begin to construct models of T cell recognition. Another area of research which has exploded over the past five years has been the identification of MHC-associated peptides. There are several methods one can use to determine the sequence identity of MHC restricted peptides. Historically, the most successful technique, albeit crude and encumbered with serious limitations, has been the use of overlapping synthetic peptides and T cell clones. Unfortunately, this method absolutely requires: (i) knowledge of the target antigen; (ii) availability of T cell clones; and (iii) a relatively short overall length for the target source protein, such that a set of overlapping pep tides can be affordably synthesized. Briefly, the entire sequence of the tar get protein is chemically synthesized using overlapping peptides which are then screened for biological activity using standard T cell presen tation assays. Despite its limitations, this method was used to identify the first immunodominant epitopes reported in the literature and con tinues to be used successfully today.

1. Major Histocompatibility Antigens: An Introduction.- 2. The Major Histocompatibility Complex Genes and Their Transcriptional Regulation.- The Murine Major Histocompatibility Complex.- The Major Histocompatibility Complex of Humans, the HLA.- Developmental and Tissue-Specific Expression of MHC Genes.- Role of Aberrant Expression of MHC Gene Products in Immunologic Disease.- Cis-Elements and Transcription Factors That Control MHC Class I Gene Expression.- Factors and Elements That Control MHC Class II Gene Expression.- Models of Activation and Repression.- Concluding Comments.- 3. TAP Peptide Transporters and Antigen Presentation.- Evidence for Peptide Translocation by TAP.- Tap Genes and Sequences.- TAP as Member of the ABC Transporter Family.- Structure and Assembly of the TAP Complex.- In Vitro Assays for Peptide Binding and Transport by TAP.- Sequence Specificity of Peptide Transport by Different TAP Molecules.- Relating Specificity to the Structure of Polymorphic TAP Molecules.- Length of Transported Peptides.- TAP-Dependent and Independent Presentation.- TAP and Disease.- Concluding Remarks.- 4. Molecular Chaperones in MHC Class I and Class II Biosynthesis and Assembly.- Introduction: ER Resident Molecular Chaperones.- Molecular Chaperones Implicated in Class I Biosynthesis and Assembly.- Molecular Chaperones Implicated in MHC Class II Biosynthesis and Assembly.- Quality Control of MHC Molecules Mediated by Molecular Chaperones.- 5. Polypeptide Release from Lysosomes.- Synthesis and Transport of Lysosomal Hydrolases.- Entry of Degradation Substrates.- Lysosomal Hydrolysis.- Polypeptide Release from Lysosomes.- Possible Immunological Relevance.- Conclusion.- 6. Intracellular Trafficking of MHC Class II Molecules.- Assembly of MHC Class II Molecules in the ER and Early Stages of Transport.- Processing Intermediates of Invariant Chain.- Post-Golgi Trafficking of MHC Class II Molecules and Sites of Invariant Chain Degradation.- Intracellular Sites of Assembly of Peptide:MHC Class II Complexes.- 7. The Role of HLA-DM in Class II Antigen Presentation.- DM Sequence and Structure.- Regulation of Expression.- Genomic Organization of DM Genes.- Evolutionary Considerations.- DM Polymorphism.- Analysis of DM Mutant Cells.- The Mechanism of DM Action.- The Biology of Antigen Processing.- The Biosynthesis and Maturation of Class II.- Conclusion.- 8. Crystallographic Analysis of Peptide Binding by Class I and Class II Major Histocompatibility Antigens.- Class I Major Histocompatibility Antigens.- Class II Major Histocompatibility Antigens.- Similarities and Differences Between Class I and Class II Major Histocompatibility Antigens.- 9. HLA and Disease: Molecular Basis.- Tissue Typing Techniques.- Epidemiological Analysis.- Paradigms of Diseases Associated with the MHC.- HLA-B27 and Ankylosing Spondylitis.- MHC II and Disease.- Concluding Remarks.- 10. Epitope Prediction Algorithms for Class I MHC Molecules.- Elucidation of Peptide-Binding Motifs.- Anchor Residues.- Peptide-Binding Assays.- Physical Basis for Peptide-Binding Motifs.- Prediction of Binding Peptides.- Exceptional Peptides.- Peptide Binding and Antigenicity.- Conclusions.- 11. Options for TCR Interactions: TCR Agonists, Antagonists and Partial Agonists.- Introduction: Smart and Dumb T Cell Receptors.- Full Agonists, Partial Agonists and Antagonists.- What Do TCR Partial Agonists and Antagonists Do?.- T Cell Development.- The Direction of Mature T Cell Responses.- The Two Edged Sword: Antagonists as Protectors and Perpetrators of Disease.- How Do Antagonist/Partial Agonists Work?.- Concluding Remarks.- 12. Role of Ligand Density in T Cell Reactions.- Background.- The Study of Peptides Recognized by CD8+ CTL.- What Determines the Efficacy of CTL-Mediated Target Cell Lysis?.- Role of Ligand Density.- Concluding Remarks.- 13. Cooperative Recognition of MHC Class II Molecules:Peptide Complexes by the T Cell Receptor and CD4.- TCR Recognition of MHC Class II:Peptide Complexes.- CD4 Binding to MHC Class II Molecules.- CD4 Interaction With the TCR:CD3 Complex.- Conclusions.- 14. Receptors for MHC Class I Molecules in Human Natural Killer Cells.- MHC Class I Molecules Inhibit NK Cell Cytotoxicity.- Murine NK Inhibitory Receptors.- Human NK Inhibitory Receptors.- A New Family of Immunoglobulin-Superfamily (Ig-SF) Genes Selectively Expressed in Human NK Cells.- Evidence That NK-Specific Ig-SF Genes May Encode Human Receptors for Class I Molecules.- NK Recognition of MHC Class I Molecules Is Mediated by a Complex System.- 15. The MHC in Host-Pathogen Evolution.- Selection Acting on the Human Host.- Pathogen Avoidance of T Cell Recognition.- Mechanisms of Decreasing Antigen Presentation.- Mechanisms of Avoiding T Cell Recognition of Specific Epitopes.- Perspective.- 16. Peptide-Mediated Regulation of Allergic Diseases.- The Role of CD4+ T Cell Subsets.- The Immunological Objectives of Allergy Therapy.- Regulation of Specific T Cells by Peptides.- Deviation of Thl/Th2 Phenotype of the Responder Population.- 17. Genetic Modulation of Antigen Presentation.- Vaccines.- Genetic Immunization for Viral Diseases.- Treatment of Autoimmune Disease.- Conclusion.

Erscheinungsdatum	20.12.2018
Zusatzinfo	37 Illustrations, color; 52 Illustrations, black and white; 89 illus., 37 illus. in color.
Verlagsort	New York, NY
Sprache	englisch
Maße	216 x 280 mm
Themenwelt	Schulbuch / Wörterbuch
	Geisteswissenschaften
	Sozialwissenschaften
Schlagworte	Antigen • Antigen presentation • autoimmune disease • Cognition • Cytotoxicity • Diseases • Evolution • Histocompatibility • Identity • immunization • Immunoglobulin • Research • T Cell • Vaccine
ISBN-10	1-4684-6464-7 / 1468464647
ISBN-13	978-1-4684-6464-1 / 9781468464641
Zustand	Neuware