CD4-independent T cells impair TCR triggering of CD4-dependent T cells: a putative mechanism for T cell affinity maturation

In vivo, T cells expressing low-affinity TCR predominate in primary, but no t in secondary responses, a process referred to as T cell affinity maturati on. Using CD4 dependence as a measure of the avidity of the interaction bet ween the allospecific TCR and the alloantigen, we show that a similar proce ss occurs in mixed lymphocyte cultures in vitro. Moreover, in coculture exp eriments high-avidity (CD4-independent)T cell clones inhibited the TCR inte rnalization of low-avidity (CD4-dependent)T cell clones, whereas low-avidit y T cell clones had no such effect on high-avidity T cell clones. The exten t of inhibition of TCR internalization was dependent on both the avidity of the competing clone and the number of competing cells. Thus, there was a c ell dose- and avidity-dependent effect on TCR internalization, an early par ameter in T cell activation. These results suggest that low- and high-avidi ty T cell clones compete for the availability of antigen-presenting cells a nd that this favors the selective outgrowth of high-avidity T cell clones.