THE V-REGION DISEASE HYPOTHESIS - NEW EVIDENCE SUGGESTS IT IS PROBABLY WRONG

Repertoire analyses of activated T-cell populations specific for myeli n basic protein, peptides of which cause experimental allergic encepha lomyelitis in rats and mice, indicate a very limited utilization of ho mologous V(alpha) and V(beta) genes in both species. However, the ence phalitogenic peptide fragments of myelin basic protein represent diffe rent domains of the antigen molecule and the MHC restricting elements are different. This finding has lead to an interpretation, the 'V-regi on disease hypothesis', which suggests that some TCR molecules may hav e special effector functions in addition to peptide-MHC recognition. O n the basis of recent findings with the rat experimental allergic ence phalomyelitis model and preliminary studies in human multiple sclerosi s, we present a more conservative and conventional interpretation of t he association of certain TCR V-region elements with encephalitogenici ty.