MHC Molecules : Expression, Assembly and Function

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. Front Matter....Pages i-xi Major Histocompatibility Antigens: An Introduction....Pages 1-8 The Major Histocompatibility Complex Genes and their Transcriptional Regulation....Pages 9-34 TAP Peptide Transporters and Antigen Presentation....Pages 35-63 Molecular Chaperones in MHC Class I and Class II Biosynthesis and Assembly....Pages 65-71 Polypeptide Release from Lysosomes....Pages 73-82 Intracellular Trafficking of MHC Class II Molecules....Pages 83-96 The Role of HLA-DM in Class II Antigen Presentation....Pages 97-111 Crystallographic Analysis of Peptide Binding by Class I and Class II Major Histocompatibility Antigens....Pages 113-134 HLA and Disease: Molecular Basis....Pages 135-162 Epitope Prediction Algorithms for Class I MHC Molecules....Pages 163-180 Options for TCR Interactions: TCR Agonists, Antagonists and Partial Agonists....Pages 181-190 Role of Ligand Density in T Cell Reactions....Pages 191-206 Cooperative Recognition of MHC Class II:Peptide Complexes by the T Cell Receptor and CD4....Pages 207-228 Receptors for MHC Class I Molecules in Human Natural Killer Cells....Pages 229-241 The MHC in Host-Pathogen Evolution....Pages 243-260 Peptide-Mediated Regulation of Allergic Diseases....Pages 261-279 Genetic Modulation of Antigen Presentation....Pages 281-294 Back Matter....Pages 295-298 This text covers various gene products of the major histocompatibility complex from transcription to disease association and therapeutic regulation of the cellular immune response.