UC Berkeley

CD8 T cells restricted to the nonclassical MHC 1 (MHC 1b) molecule MHC-E show great promise in vaccine settings, but the development and specificity of MHC-E restricted T cells remains poorly understood. Here we focus on a CD8 T cell population reactive to a self-peptide (FL9) bound to mouse MHC-E (Qa1b) that is presented in response to loss of the classical (MHC 1a) processing enzyme ERAAP, termed QFL T cells. We find that mature QFL thymocytes are predominantly CD8+CD4-, show signs of agonist selection, and give rise to both CD8 and CD8 intraepithelial lymphocytes (IEL), as well as circulating memory phenotype CD8 T cells. QFL T cells require the MHC 1 subunit -2 microgloblin (2m), but do not require Qa1b or epithelial MHC 1 for positive selection. However, QFL thymocytes do require Qa1b for agonist selection and full functionality. Our data highlight the relaxed requirements for positive selection of an MHC-E restricted T cell population, and suggest a CD8+CD4- pathway for development of CD8 IELs.