Antigen-specific depletion of CD4+T cells by CART T cells reveals distinct roles of higher- and lower-affinity TCRs during autoimmunity, 2022, JAEU YI

Engineering CAR T cells to target autoimmunity
Autoimmune diseases including multiple sclerosis (MS) are driven by pathogenic CD4+ T cells that recognize self-antigens. Yi et al. engineered chimeric antigen receptor (CAR) T cells to recognize and kill self-reactive T cells by introducing a peptide-MHCII (pMHCII) domain. Their original pMHCII-CAR design efficiently deleted T cells bearing a higher-affinity T cell receptor, whereas further modifications to enhance pMHCII stability and in vivo survival enabled simultaneous targeting of lower-affinity T cells.

In a mouse experimental autoimmune encephalomyelitis model of MS-like disease, deletion of higher-affinity T cells was sufficient to prevent disease onset, whereas targeting lower-affinity T cells was necessary to reverse ongoing disease.

These findings highlight strategies for designing CAR T cells to target distinct stages of autoimmune disease.

https://www.science.org/doi/10.1126/sciimmunol.abo0777?cookieSet=1