Post-proteasomal antigen processing for major histocompatibility complex class I presentation.
Peptides presented by major histocompatibility complex class I molecules are derived mainly from cytosolic oligopeptides generated by proteasomes during the degradation of intracellular proteins. Proteasomal cleavages generate the final C terminus of these epitopes. Although proteasomes may produce mature epitopes that are eight to ten residues in length, they more often generate N-extended precursors that are too long to bind to major histocompatibility complex class I molecules. Such precursors are trimmed in the cytosol or in the endoplasmic reticulum by aminopeptidases that generate the N terminus of the presented epitope. Peptidases can also destroy epitopes by trimming peptides to below the size needed for presentation. In the cytosol, endopeptidases, especially thimet oligopeptidase, and aminopeptidases degrade many proteasomal products, thereby limiting the supply of many antigenic peptides. Thus, the extent of antigen presentation depends on the balance between several proteolytic processes that may generate or destroy epitopes.
Rock
Kenneth L
KL
Department of Pathology, University of Massachusetts Medical Center, Worcester, MA 01655, USA.
York
Ian A
IA
Goldberg
Alfred L
AL
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D003546:Cysteine Endopeptidases / Q000276:immunology / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000939:Epitopes / Q000276:immunology / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D009097:Multienzyme Complexes / Q000276:immunology / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex
D000939:Epitopes; D015395:Histocompatibility Antigens Class I; D009097:Multienzyme Complexes; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex