Post-proteasomal antigen processing for major histocompatibility complex class I presentation

KL Rock, IA York, AL Goldberg - Nature immunology, 2004 - nature.com
KL Rock, IA York, AL Goldberg
Nature immunology, 2004nature.com
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 …
Abstract
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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