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.

LCMV infection of adult B6 mice generates a robust CD8 T cell response, peaking at 8 or 9 d after infection and eventually establishing a stable virus-specific CD8 memory T cell pool (17, 18) , where Ͼ 20% of the CD8 T cells in the PBLs can be identified as specific to LCMV-encoded epitopes (Fig. 1, A and B) . The hierarchy of responses against different epitopes is very similar between immunologically naive mice ( Fig. 1 and reference 17 ), but the integrity of the LCMV epitope-specific memory CD8 T cell pool is often disrupted by heterologous viral infections, which preferentially expand cross-reactive T cells while deleting noncrossreactive ones (2, 19, 20) . We have elaborated the impacts of two heterologous viruses (PV and VV) on LCMV-immune mice and found that these two viruses generated characteristic and contrasting patterns of T cell responses to epitopes in LCMV-immune mice (2) (3) (4) . PV and LCMV share strongly cross-reactive subdominant epitopes (PV-NP205 and LCMV-NP205) that dominate the immune response when these viruses are infected in sequence ( Fig. 1 A and reference 2). In contrast, VV infection of LCMV-immune mice exhibits a much less predictable pattern, where the specificity of expanded T cells is not always the same between experiments ( Fig. 1 B and references 3, 4) .