MHC basis of T cell-dependent heterologous immunity to arenaviruses

Highlight
- Heterologous immunity between LCMV and Pichinde virus (PV) was MHC dependent.
- Heterologous immunity between LCMV and PV was a specific phenomenon.
- CD8 T cell cross-reactivity was demonstrated between LCMV and PV in H2d mice.
- LCMV and PV encode putative Ld-restricted NP313-NP322 epitopes.
- The NP313 epitopes of LCMV and PV are cross-reactive with CD8 T cells.

Having a history of infection with one pathogen may sometimes provide a level of T cell-dependent protective heterologous immunity to another pathogen. This immunity was initially thought due to cross-reactive T cell epitopes, but recent work has suggested that such protective immunity can be initiated nonspecifically by the action of cytokines on memory T cells. We retested this concept using two small and well-defined arenaviruses, lymphocytic choriomeningitis virus (LCMV) and Pichinde virus (PV), and found that heterologous immunity in these systems was indeed linked to T cell epitopes and the major histocompatibility complex.