Expansion of CD4 T cells expressing a highly restricted TCR structure specific for a single parasite epitope correlates with high pathology in murine schistosomiasis.

The hepatic immunopathology in schistosomiasis mansoni is mediated by CD4 T cells specific for egg antigens and varies considerably among mouse strains. Previous studies in high pathology C3H mice suggested that a strong T cell response was due to the recognition of an immunodominant epitope within the major egg antigen Sm-p40 (Sm-p40(234-246)). Using a panel of T cell hybridomas, we have now examined the egg antigen-specific TCR repertoire in two high pathology strains, C3H and CBA. We found that nearly half of the hybridomas responded to the Sm-p40(234-246 )epitope and, of these, nearly all expressed Valpha11.3 associated with Vbeta8. Furthermore, in response to egg antigen stimulation, transcript levels of Valpha11.3J36 (the most prevalent rearrangement expressed by Sm-p40(234-246)-specific hybridomas), increased in high pathology (CBA) but not in low pathology BALB/c strains. Our findings suggest that exacerbated schistosome egg-induced immunopathology can be driven by T cells expressing a highly restricted TCR structure specific for a single parasite epitope.