The V-region disease hypothesis: new evidence suggests it is probably wrong.

Repertoire analyses of activated T-cell populations specific for myelin basic protein, peptides of which cause experimental allergic encephalomyelitis in rats and mice, indicate a very limited utilization of homologous V alpha and V beta genes in both species. However, the encephalitogenic peptide fragments of myelin basic protein represent different domains of the antigen molecule and the MHC restricting elements are different. This finding has lead to an interpretation, the 'V-region disease hypothesis', which suggests that some TCR molecules may have special effector functions in addition to peptide-MHC recognition. On the basis of recent findings with the rat experimental allergic encephalomyelitis model and preliminary studies in human multiple sclerosis, we present a more conservative and conventional interpretation of the association of certain TCR V-region elements with encephalitogenicity.