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.

Under conditions of heterologous immunity, T cell responses are sometimes uniformly directed against strongly cross-reactive epitopes, such as between LCMV and PV. However, in other cases, patterns of heterologous immunity and T cell cross-reactivity may be variable, such as between LCMV and vaccinia virus (VV). A history of an LCMV infection protects mice against VV, reducing VV titers 10-100-fold by day 3 after infection, and dramatically changing the T cell-dependent immunopathology (1, 3) . Adoptive transfer studies indicated that LCMV-immune CD4 and CD8 T cells provided heterologous immunity in this system (1) . Ironically, a history of a VV infection has little effect on immunity to LCMV (1) . VV induces the proliferation of some LCMV-specific memory T cells, but LCMV does not induce detectable proliferation of VV-specific memory T cells (4) . A possible explanation to this enigma is that VV is a virus that encodes Ͼ 200 proteins and perhaps Ͼ 1,000 T cell epitopes with the capacity to trigger memory T cells present at sufficient frequencies. In contrast, LCMV encodes only four proteins. Thus, it seems that the many potential epitopes encoded by VV would more likely stimulate some T cells in an LCMV-specific memory pool than would the much more limited number of LCMV epitopes stimulating a VV-immune pool.