The nonclassical immune surveillance for ERAAP function

Abstract

The peptide repertoire presented by MHC class I molecules on the cell surface is essential for the immune surveillance of intracellular pathogens and transformed cells. The generation of this peptide repertoire is critically dependent on the endoplasmic reticulum aminopeptidase associated with antigen processing (ERAAP). Loss of ERAAP function leads to the generation of a profoundly disrupted peptide repertoire including many novel and immunogenic peptides. Strikingly, a large fraction of these novel peptides on ERAAP-KO cells are presented by the nonclassical MHC Ib molecule, Qa-1^b. One immunodominant Qa-1^b-restricted novel peptide is recognized by a unique CD8⁺ T cell population showing features of both conventional cytotoxic T cells and unconventional innate-like T cells. While much remains to be uncovered, here we summarize the latest discoveries of our lab on the important immune surveillance of ERAAP function mediated by nonclassical MHC Ib molecules and their unusual cognate T cells.