The cell biology of antigen processing and presentation.
Histocompatibility molecules are peptide-binding proteins and present antigenic peptides to T cells. In spite of similarity in structure and peptide specificity, class-I and class-II histocompatibility molecules present peptides at different intracellular locations. Class-I molecules present peptides derived from endogenous proteins, but class-II molecules can present peptides from endocytosed (exogenous) antigen as well as endogenous antigen. Binding of antigenic peptides by histocompatibility molecules is a function of their assembly, intracellular trafficking, and endocytosis. For class-I molecules, assembly appears to be the most important step for peptide acquisition, while all three processes can potentially influence class-II antigen presentation. The versatility of peptide binding by class-II MHC molecules is due to its association with the invariant chain which blocks peptide binding during the initial stages of class-II assembly and export and contributes to the endosomal targeting of class-II molecules. Once invariant chain dissociates, class-II molecules become competent to bind peptides and are released to the cell surface. The location in which a particular antigenic peptide is produced is a function both of its route of introduction into the cell and its susceptibility to degradation. These factors contribute significantly to whether an antigen will be presented by class-I or class-II molecules and should be taken into account in the design and development of vaccines.
Brodsky
F M
FM
Department of Pharmacy, University of California, School of Pharmacy, San Francisco 94143.
Guagliardi
L E
LE
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism; D004705:Endocytosis; D010450:Endopeptidases / Q000378:metabolism; D006649:Histocompatibility Antigens / Q000378:metabolism*; D006801:Humans; D010455:Peptides / Q000378:metabolism
D006649:Histocompatibility Antigens; D010455:Peptides; D010450:Endopeptidases