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.

The VV-induced expansions in LCMV epitope-specific T cells predict that there may be cross-reactive epitopes between VV and LCMV, and the high incidence of expansion of T cells specific to the NP205 epitope suggests that VV may encode epitopes cross-reactive with NP205. We have identified several VV-encoded amino acid sequences harboring K b binding motifs and partial homology with NP205 (unpublished data). One VV-encoded epitope, generated from VV protein A11R (198-205), has 4/8 amino acids in common with NP205 and 3/8 amino acids in common with GP34-41 and GP118. Subpopulations of T cells specific to the A11R198 epitope cross-react with GP34 and GP118 and, to a lesser extent, with NP205. As an example, Fig. 4 A presents CD8 T cells from an VV A11R198 peptide-stimulated cell line derived from an LCMV-immune mouse and shows that a subpopulation of them costain with tetramers charged with A11R198 and GP118 peptides. A11R is detected by a low percentage of T cells from LCMV-immune mice (mean Ï­ 0.33% Ï® 0.1, n Ï­ 9) and to a lesser extent in VV acutely infected (day 6) mice (mean Ï­ 0.23% Ï® 0.19, n Ï­ 17). The frequency of A11R 198-specific CD8 T cells was on average significantly higher (mean Ï­ 0.55% Ï® 0.59, n Ï­ 29) after a day 6 VV infection of LCMV-immune mice (P Ï­ 0.03), but was highly variable, suggesting a private specificity phenomenon.