A novel effect of the antigenic peptides position for presentation upon MHC class I

MHC-I molecules are expressed on the cell surface complexed with oligopeptides, most of which are generated from intracellular proteins by the ubiquitin-proteasome pathways and would be roughly proportional to the relative abundance of proteins and their rate of degradation. Thus MHC-I together with peptides function as immunological self-markers to exhibit the information about the repertoire of proteins expressed in a given cell to the immune system, and this process is called antigen (Ag) direct-presentation. Herein, we report a novel rule for the preference of peptides selected for the direct presentation; the N-terminally located antigenic peptides are more efficiently complexed with MHC-I than the C-terminally located peptides on the same protein. The superiority is largely dependent upon de novo proteins synthesis, degradation by proteasomes, and less dependent upon stabilities of proteins, indicating that this difference derived from rapidly degraded newly synthesized proteins such as defective ribosomal products (DRiPs). The effects of those N-terminal predominance was comparable with the enhanced MHC-I presentation by IFN-γ suggesting that they might play important roles in the adaptive immunity.