Rock Kenneth L, York Ian A, Goldberg Alfred L
Department of Pathology, University of Massachusetts Medical Center, Worcester, MA 01655, USA.
Nat Immunol. 2004 Jul;5(7):670-7. doi: 10.1038/ni1089.
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.
主要组织相容性复合体I类分子呈递的肽主要源自蛋白酶体在细胞内蛋白质降解过程中产生的胞质寡肽。蛋白酶体切割产生这些表位的最终C末端。尽管蛋白酶体可能产生长度为8至10个残基的成熟表位，但它们更常产生N端延伸的前体，这些前体太长而无法与主要组织相容性复合体I类分子结合。此类前体在胞质溶胶或内质网中被氨肽酶修剪，从而产生呈递表位的N末端。肽酶也可通过将肽修剪至低于呈递所需的大小来破坏表位。在胞质溶胶中，内肽酶，尤其是硫醇寡肽酶和氨肽酶会降解许多蛋白酶体产物，从而限制了许多抗原肽的供应。因此，抗原呈递的程度取决于可能产生或破坏表位的几种蛋白水解过程之间的平衡。
