Physiological and Functional Effects of Dominant Active TCRα Expression in Transgenic Mice

A T cell receptor (TCR) consists of a- and b-chains. Accumulating evidence suggests that some TCRs possess chain centricity, i.e., either of the hemi-chains can dominate in antigen recognition and dictate the TCR's specificity. The introduction of TCRa/beta into naive lymphocytes generates antigen-specific T cells that are ready to perform their functions. Transgenesis of the dominant active TCRa creates transgenic animals with improved anti-tumor immune control, and adoptive immunotherapy with TCR alpha-transduced T cells provides resistance to infections. However, the potential detrimental effects of the dominant hemi-chain TCR's expression in transgenic animals have not been well investigated. Here, we analyzed, in detail, the functional status of the immune system of recently generated 1D1a transgenic mice expressing the dominant active TCR alpha specific to the H2-K-b molecule. In their age dynamics, neither autoimmunity due to the random pairing of transgenic TCR alpha with endogenous TCR beta variants nor significant disturbances in systemic homeostasis were detected in these mice. Although the specific immune response was considerably enhanced in 1D1a mice, responses to third-party alloantigens were not compromised, indicating that the expression of dominant active TCR alpha did not limit immune reactivity in transgenic mice. Our data suggest that TCR alpha transgene expression could delay thymic involution and maintain TCR beta repertoire diversity in old transgenic mice. The detected changes in the systemic homeostasis in 1D1a transgenic mice, which are minor and primarily transient, may indicate variations in the ontogeny of wild-type and transgenic mouse lines.