Endogenous co-expression of two T cell receptors promotes lymphopenia-induced proliferation via increased affinity for self-antigen

Journal of Leukocyte Biology
Amritha BalakrishnanGerald P Morris

Abstract

Approximately 10% of peripheral T cells express 2 functional TCR αβ heterodimers. Receptor co-expression changes the repertoire of TCRs produced during thymic development, enabling generation of T cells bearing TCRs not capable of mediating positive selection or that would normally be negatively selected. The effect of receptor co-expression on the composition and functionality of the peripheral TCR repertoire is not well defined, though evidence demonstrates dual TCR cells pose an increased risk for unwanted immune responses such as autoimmunity and alloreactivity. Based on our previous finding that dual TCR expression promotes positive selection, we hypothesized that dual TCR expression may enhance T cell homeostasis via increased reactivity against self-peptide:MHC (pMHC) ligands. To examine the effect of dual TCR expression on T cell homeostasis, we performed cotransfer experiments comparing T cells genetically deficient for dual TCR expression (TCRα+/- ) with wild-type T cells in models of acute and chronic lymphopenia-induced proliferation (LIP). Lack of dual TCR expression resulted in reduced LIP. The effect of dual TCR expression on LIP was most pronounced in acute lymphopenia, which is driven by recognition of low-affi...Continue Reading

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Citations

Dec 9, 2020·Proceedings of the National Academy of Sciences of the United States of America·Letitia YangGerald P Morris

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