High affinity T cell receptor gives advantage to the homeostatic proliferation of naive CD8 T cells only under competitive pressure (126.28)

Abstract The impact of T cell receptor (TCR) affinity during homeostatic proliferation has been demonstrated using naive CD8+ T cells with high and low affinity TCR derived from different precursors. In this study, we investigated the impact of TCR affinity using cells derived from the same precursor and selected under the same conditions, namely Pmel TCR transgenic (vβ13) naive CD8+ T cells, which respond to both high (hgp100) and low (mgp100) affinity peptides. Contrary to previous reports, we found that exposure of naive Pmel cells to either high or low-affinity peptide resulted in similar levels of homeostatic proliferation. However, in the presence of OT-1 cells and their cognate peptide (SINFKL), the levels of homeostatic proliferation of Pmel cells were higher after exposure to hgp100 than to mgp100 (1.85 vs 1.25 on day 8, 2.06 vs 1.20 on day 11, 2.57 vs 1.30 on day 15, 2.35 vs 0.89 on day 22). Interestingly, expression levels of memory markers (CD44lo to CD44hi, CD122lo to CD122hi and CD62Lhi to CD62Lhi) were similar under both circumstances. Overall, these results suggest that the difference seen in the effect of high-affinity TCR compared with low-affinity TCR on CD8+ cell expansion during homeostatic proliferation occurs only in the presence of competitive pressure. This difference may be balanced by a higher availability of low-affinity antigen, and thus may have important implications for vaccine design in the post-transplant setting.