Genetic control of T-cell proliferative response in mice linked to chromosomes 11 and 15

Antigen-induced activation of T lymphocytes plays a central role in specific immune reactions. This response is influenced by antigen presenting cells and depends on T-cell signalling pathways (Wegener et al. 1992; Jenkins and Johnson 1993; Howe and Weiss 1995). T cells can be stimulated to produce cytokines and cytokine receptors which drive proliferation and differentiation, and to express cell surface and intracellular molecules involved in effector functions. As intracellular events initiated by the ligation of the alpha / beta heterodimer of the T-cell receptor (TCR) are mediated by signal transduction through the CD3 complex, the CD3 monoclonal antibody (mAb) is widely used as a trigger for the analysis of T-cell activation. Mouse strains BALB/cHeA (BALB/c) and STS/A (STS) differ in their response to CD3 antibody; lymphocytes of the strain BALB/c are high responders, whereas STS lymphocytes do not respond to this stimulus. This deficient response is due to the STS allele at the Fcgr2 locus which produces a non-functional CD32 (Fc gamma receptor 2) molecule. To analyze whether other gene(s) influence the response to mAb CD3 as well, we used the recombinant congenic strains (RCS) of the BALB/c-c-STS/Dem (CcS/Dem) series, which have been developed for genetic analysis of multigenically-controlled complex biological processes.