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.
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We thank E. Bishop for assistance in preparation of this manuscript. Supported by grants from the National Institute of General Medical Sciences (A.L.G.) and National Institutes of Health (K.L.R.).
The authors declare no competing financial interests.
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Rock, K., York, I. & Goldberg, A. Post-proteasomal antigen processing for major histocompatibility complex class I presentation. Nat Immunol 5, 670–677 (2004) doi:10.1038/ni1089
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