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Bi-Allelic TCR or Recombination Enhances T Cell Development but Is Dispensable for Antigen Responses and Experimental Autoimmune Encephalomyelitis

Schuldt, NJ;Auger, JL;Hogquist, KA;Binstadt, BA;

Dual TCR-expressing T cells outnumber dual TCR-expressing cells by ~10:1. As a result, efforts to understand how dual TCR T cells impact immunity have focused on dual TCR expression; dual TCR expression remains understudied. We recently demonstrated, however, that dual TCR expression accelerated disease in a TCR transgenic model of autoimmune arthritis through enhanced positive selection efficiency, indicating that dual TCR expression, though rare, can impact thymic selection. Here we generated mice hemizygous for TCR, TCR, or both on the C57BL/6 background to investigate the impact bi-allelic TCR chain recombination has on T cell development, repertoire diversity, and autoimmunity. Lack of bi-allelic TCR or TCR recombination reduced thymocyte development efficiency, and the absence of bi-allelic TCR recombination promoted T cell development. However, we observed no differences in the numbers of nave and expanded antigen-specific T cells between TCR+/-+/- and wildtype mice, and TCR repertoire analysis revealed only subtle differences in V gene usage. Finally, the absence of dual TCR T cells did not impact induced experimental autoimmune encephalomyelitis pathogenesis. Thus, despite more stringent allelic exclusion of TCR relative to TCR, bi-allelic TCR expression can measurably impact thymocyte development and is necessary for maintaining normal / T cell proportions.