The Effect of Nominal Antigen and Ia Molecule Concentrations on the Magnitude of the Proliferative Response of T Cell Clones

Activation of antigen-specific regulatory T lymphocytes requires concomitant recognition of both the nominal (foreign) antigen and self Ia molecules. The response of T cells specific for the globular protein antigen pigeon cytochrome c in H-2 congenic B10.A (H-2a) and B10.S (9R)(H-2t4) mice has previously been shown to occur in the context of the homologous I-A/E β k :I-E α k and I-A/E β s :I-E α k Ia molecules, for which the beta (β) chains are encoded within the I-A subregion and the alpha (α) chains are encoded within the I-E subregion of the H-2 gene complex (1). Furthermore, the magnitude of the in vitro proliferative response of pigeon cytochrome c-specific long term T cell lines was shown to be a function of both the nominal antigen concentration and the amount of Ia molecules expressed on the antigen presenting cell (APC) (2). An interesting aspect of the dose-response curves obtained with these lines was an observed decrease in responsiveness at high antigen concentrations. Pigeon cytochrome c-specific T cell clones were derived from the long term lines and the antigen dose response curves of these clones were also consistently characterized by a peak proliferation followed by a decrease in the magnitude of the proliferative response at higher antigen concentrations (3). An example of this phenomenon is shown by the data in Figure 1, which represent the antigen dose responses of B10.A T cell clone A3.G4 in the presence of B10.A and B10.S(9R) APCs.