Endoplasmic reticulum aminopeptidase 1 (ERAP1) trims MHC class I-presented peptides in vivo and plays an important role in immunodominance

摘要: CD8+ T cells respond to short peptides bound MHC class I molecules. Although most antigenic proteins contain many sequences that could bind I, few of these actually stimulate cell responses. Moreover, the responses are generated often follow a very reproducible hierarchy different for reasons poorly understood. We find loss single enzyme, endoplasmic reticulum aminopeptidase 1 (ERAP1), in antigen-processing pathway results marked shift immunodominance viral infections, even when responding have same receptor repertoire. In mice, ERAP1 is major enzyme trims precursor and, this process, can generate or destroy peptides. Consequently, lost, immune response some reduced, others increased, and yet unchanged. Therefore, epitopes must be initially as precursors normally trimmed by before binding whereas degraded lengths too I. peptide trimming resulting abundance peptide–MHC complexes dominant factors establishing immunodominance.