Private specificities of CD8 T cell responses control patterns of heterologous immunity

Kim, Sung-Kwon; Cornberg, Markus; Wang, Xiaoting Z.; Chen, Hong D.; Selin, Liisa K.; Welsh, Raymond M.

This trend toward epitope preference in an otherwise difficult-to-predict heterologous immune response was more consistent with a TCR-based cross-reactivity phenomenon than with a nonspecific TCR-independent bystander phenomenon. As a technique to support the concept of a TCRmediated event, we examined the down-regulation of IL-7 receptors (IL-7R ␣ ) on CD8 T cells. Virus-specific CD8 T cells in the memory phase express high levels of IL-7R ␣ , but these become down-regulated on TCR cross-linking. The majority of LCMV-specific memory CD8 T cells are IL-7R ␣ hi (Fig. 2) , but after secondary LCMV challenge in vivo, Ͼ 50% of the LCMV-specific CD8 T cells of various specificities uniformly down-regulated IL-7R ␣ on their surface (Fig. 2, top left quadrant) . In contrast, LCMV-immune mice challenged with PV down-regulated IL-7R ␣ only on the highly cross-reactive NP205-specific T cells (unpublished data). Interestingly, with a VV challenge, the pattern varied between mice. IL-7R ␣ down-regulation was 23-42% in some mice (nos. 1 and 2) on GP33/34-specific T cells, on another mouse on GP118-specific T cells (no. 3), and on another on NP205-specific T cells (no. 2) (Fig. 2, no. 2). All other epitope-specific responses were Յ 12%, suggesting very low, if any, TCR stimulation. VV-stimulated LCMV-specific T cells were examined for forward scatter, as an indicator of cell size with regard to IL-7R ␣ . The cells low in IL-7R ␣ expression were larger, as indicated by substantially increased forward scatter (e.g., GP33-specific CD8 T cells in no. 2 mouse, FSC of IL-7R low ϭ 402 vs. high ϭ 344). These data are consistent with the concept that the T cells are being stimulated through their TCR and, thus, probably proliferating even though the epitope specificity varies between mice.