Cellular mechanisms of antigen processing and the function of class I and II major histocompatibility complex molecules.

Antigen recognition: an overview Antigen recognition in humoral immunity has long been understood: the antigen-specific (Fab) portion of the antibody molecule binds directly to the antigen in its native state.The antibody molecules are found as antigen receptors on the plasma membrane of B cells and also as secreted proteins.In contrast, the biochemical basis for antigen recognition by T cells has only recently become clear.In general, T cells do not recognize antigens in their native conformation, but only after partial proteolysis within antigen processing or presenting cells (APC) into con- stituent peptides that bind to molecules en- coded by genes in the major histocompatibility complex (MHC).The bimolecular complex of antigen peptide and MHC molecule is then dis- played on the APC plasma membrane to be recognized by T-cell clones bearing a specific antigen receptor for it.This recognition leads to their stimulation and proliferation.The MHC molecules are, therefore, peptide carriers that serve to rescue peptides from extensive intra- cellular catabolism, making them available to the T-cell system (Unanue and Allen, 1987).They also constitute part of the antigenic de- terminant that T cells have evolved to recognize.Antigen presentation, therefore, includes a novel cell biological phenomenon: that a product from internal degradation of an exogenous pro- tein becomes biologically active and recognized by another set of cells.Two classes of MHC molecules function in antigen presentation.The class I molecules (MHC-1) include HLA-A, -B, and -C in humans Review and H-2K, D, and L in mice.The class 11 mole- cules (MHC-11) include HLA-DP, -DQ, and -DR in humans and the I-A and l-E molecules in mice.This review will focus primarily on MHC-11 function, but it also discusses and compares the function of MHC-1 molecules.More extensive historical background is available in previous reviews (Unanue and Allen, 1987), whereas some recent advances are summarized elsewhere (Moller, 1987(Moller, , 1988)).