The promiscuous development of an unconventional Qa1^b-restricted T cell population

Abstract

MHC-E restricted CD8 T cells show promise in vaccine settings, but their development and specificity remains poorly understood. Here we focus on a CD8 T cell population reactive to a self-peptide (FL9) bound to mouse MHC-E (Qa-1b) that is presented in response to loss of the MHC I processing enzyme ERAAP, termed QFL T cells. We find that mature QFL thymocytes are predominantly CD8ab+CD4-, show signs of agonist selection, and give rise to both CD8aa and CD8ab intraepithelial lymphocytes (IEL), as well as memory phenotype CD8ab T cells. QFL T cells require the MHC I subunit b-2 microglobulin (b2m), but do not require Qa1b or classical MHC I 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 CD8ab+CD4- pathway for development of CD8aa IELs.

SARS-CoV-2 Envelope-mediated Golgi pH dysregulation interferes with ERAAP retention in cells

“…In MCMV-infected mice, QFLs proliferate, produce inflammatory cytokines, and contribute to viral restriction 16 . In naïve mice, QFL T-cells have an antigen experienced phenotype 17,18 suggesting that actively surveying ERAAP dysfunction, and by extension the integrity of the APP, is an important aspect of immune surveillance. A human QFL T-cell equivalent has not been identified.…”