The composition of a primary T cell response is largely determined by the timing of recruitment of individual T cell clones

Primary T cell responses rely on the recruitment and proliferation of antig en-specific T cell precursors. The extent of expansion of each individual T cell clone may depend on (a) its frequency before immunization, (b) its pr oliferative capacity, and (c) the time at which it first encounters its cog nate antigen. In this report, we have analyzed the relative contribution of each of these parameters to the shaping of immune repertoires in the T cel l response specific for the epitope 170-179 derived from HLA-Cw3 and presen ted by Kd. By means of hemisplenectomy, we compared immune and naive repert oires in the same animal and found that the frequency of all expanded T cel l clones was extremely low before immunization. III particular, the most ex panded clones did not derive from high-frequency precursors. In addition, r ecruited T cells were found to proliferate at the same rate, irrespective o f their T cell antigen receptor sequence. Finally, we showed that only T ce lls that encounter the antigen at early time points account for a significa nt part of the specific response. Therefore, the contribution of a T cell c lone to the immune response is mostly determined by the time of its entry i nto the immune repertoire, i.e., the time of first cell division after anti gen encounter.