RESTRICTION OF SELF-ANTIGEN PRESENTATION TO CYTOLYTIC T-LYMPHOCYTES BY MOUSE PEPTIDE PUMPS

Transport of an immunogenic self-peptide from the second domain of the mouse major histocompatibility complex (MHC) H-2K(d) class I molecule is blocked at the TAP1-TAP2 peptide pump level due to its amino acid sequence and is not presented to cytolytic T lymphocytes (CTL). We dem onstrate that first, TAP1-TAP2 pumps can restrict antigen presentation by selecting against internal peptide motifs which are not involved i n peptide binding to MHC class I molecules. Second, some molecules tar geted to the endoplasmic reticulum are processed for MHC class I prese ntation in the cytosol. Third, some abundantly expressed immunogenic s elf-peptides are cytosolically sequestered. The advantage for the host , in terms of the peripheral T cell repertoire is that the spared CTL can be used to recognize foreign antigens. It is, however, anticipated that this advantage will be exploited by pathogens to evade immune su rveillance by similar strategies.