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

Dual TCR alpha-expressing T cells outnumber dual TCR beta-expressing cells by similar to 10:1. As a result, efforts to understand how dual TCR T cells impact immunity have focused on dual TCR alpha expression; dual TCR beta expression remains understudied. We recently demonstrated, however, that dual TCR beta expression accelerated disease in a TCR transgenic model of autoimmune arthritis through enhanced positive selection efficiency, indicating that dual TCR beta expression, though rare, can impact thymic selection. Here we generated mice hemizygous for TCR alpha, TCR beta, 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 alpha or TCR beta recombination reduced alpha beta thymocyte development efficiency, and the absence of bi-allelic TCR beta recombination promotedd T cell development. However, we observed no differences in the numbers of naive and expanded antigen-specific T cells between TCR alpha(+/-)beta(+/-) and wildtype mice, and TCR repertoire analysis revealed only subtle differences in V beta 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 beta relative to TCR alpha, bi-allelic TCR beta expression can measurably impact thymocyte development and is necessary for maintaining normal alpha beta/gamma delta T cell proportions.