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.

Despite the mouse-to-mouse variation in epitope preferences after VV infection, clear patterns of epitope preference remained, with NP205 Ͼ GP33/34 Ͼ GP118 Ͼ NP396 Ͼ GP276 (Table I) . It is not clear why certain epitope-specific CD8 T cells are more frequently cross-reactive than others, although here the NP205, GP118, and GP34-41 epitopes are K b restricted, whereas the weakly stimulating NP396 and GP276 epitopes are D b restricted. It is possible that VV encodes more K b -restricted peptides that are potentially crossreactive than D b -restricted ones. The VV-encoded A11R 198 epitope is an example of such a cross-reactive epitope, whose response differed greatly between one VV-challenged LCMV-immune mouse and another. Another possibility is that the three-dimensional structures of some peptides (such as GP34-41 and NP205) are better at selecting a wider variety of T cell clones than others and, therefore, these epitope-specific CD8 T cells could be more promiscuous in their interactions with other peptides.