Thomas Ramos

Normal mouse T cells may express alternative TCR complexes containing the FcϵR γ chain (FcRγ) rather than the ζ homodimer that is present in conventional TCR complexes. While these T cells could play critical roles in regulating immunity, the role of alternative TCR complexes and their requirement for signaling molecules in T cell development remains unknown. We show thatexpression of an FcRγ transgene in ζ chain-deficient mice (FcRγTG, ζKO mice) reduced the percentage and number of CD4+ T cells present in these animals, when compared to C57BL/6 mice. Further studies of FcRγTG, ζKO mice expressing the DO11.10 TCR (DOTCR) transgene showed that, when compared to mice expressing conventional TCR complexes, the development of CD4+, DOTCR+ thymocytes was altered in mice of different MHC backgrounds and required the presence of zeta-associated protein (ZAP)-70 and lck kinases. The CD4+, DOTCR+ T cells bearing alternative TCR complexes have impaired Ca2+ flux and proliferative response to stimulation. Altogether, these results suggest that the altered development of CD4+ T cells is not due to qualitative differences in TCR-mediated signals, but more consistent with the hypothesis that it is due to reduced signaling strength mediated through the FcRγ chain containing only one immunoreceptor tyrosine-based activation motif.