Visualizing T cell competition for peptide/MHC complexes: A specific mechanism to minimize the effect of precursor frequency

In vivo antigenic competition of naive CD4(+) TCR transgenic T cells was visualized by tracking cell division. Competition reduced both recruitment into cell division and burst size per recruited precursor cell, minimizing the effect of differences in precursor frequency while maintaining the dose-response relationship with antigen. Competition was restricted to T cells of the same specificity, indicating that cells were competing for access to AS-MHC complexes rather than for Ag nonspecific factors. Moreover, the qualitative distinction between the responses to i.v. peptide and s.c. peptide/CFA was unaffected by precursor frequency. These data explain the paradoxical ability of the immune system to tailor responses to the type and dose of Ag even in individuals with large differences in initial precursor frequency.