Antigen-specific depletion of CD4⁺ T cells by CAR T cells reveals distinct roles of higher- and lower-affinity TCRs during autoimmunity.

ABSTRACT: Both higher- and lower-affinity self-reactive CD4⁺ T cells are expanded in autoimmunity; however, their individual contribution to disease remains unclear. We addressed this question using peptide-MHCII chimeric antigen receptor (pMHCII-CAR) T cells to specifically deplete peptide-reactive T cells in mice. Integration of improvements in CAR engineering with TCR repertoire analysis was critical for interrogating in vivo the role of TCR affinity in autoimmunity. Our original MOG_35-55 pMHCII-CAR, which targeted only higher-affinity TCRs, could prevent the induction of experimental autoimmune encephalomyelitis (EAE). However, pMHCII-CAR enhancements to pMHCII stability, as well as increased survivability via overexpression of a dominant-negative Fas, were required to targ

SUBMITTER: Yi J 

PROVIDER: S-EPMC9867937 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature