Loss of anti-viral immunity by infection with a virus encoding a cross-reactive pathogenic epitope

T cell cross-reactivity between different strains of the same virus,between different members of the same virus group,and even between unrelated viruses is a common occurrence. we questioned here how an intervening infection with a virus containing a sub-dominant cross-reactive t cell epitope would affect protective immunity to a previously encountered virus. pichinde virus (pv) and lymphocytic choriomeningitis virus (lcmv) encode subdominant cross-reactive np205-212 cd8 t cell epitopes sharing 6 of 8 amino acids,differing only in the mhc anchoring regions. these pmhc epitopes induce cross-reactive but non-identical t cell receptor (tcr) repertoires,and structural studies showed that the differing anchoring amino acids altered the conformation of the mhc landscape presented to the tcr. pv-immune mice receiving an intervening infection with wild type but not np205-mutant lcmv developed severe immunopathology in the form of acute fatty necrosis on re-challenge with pv,and this pathology could be predicted by the ratio of np205-specific to the normally immunodominant pv np38-45 -specific t cells. thus,cross-reactive epitopes can exert pathogenic properties that compromise protective immunity by impairing more protective t cell responses. © 2012 chen et al.