Multiple sclerosis retrovirus particles and recombinant envelope trigger an abnormal immune response in vitro, by inducing polyclonal V beta 16 T-lymphocyte activation

A retroviral element (MSRV) defining a family of genetically inherited endo genous retroviruses (HERV-W) has recently been characterized in cell cultur es from patients with multiple sclerosis (MS). To address the possible rela tionship with MS, direct detection of circulating virion RNA was proposed b ut revealed technically difficult to perform In standardized conditions, In the face of multiple endogenous HERV-W copies. A parallel approach has eva luated MSRV potential pathogenicity In relation to characteristic features of multiple sclerosis, in particular, T-lymphocyte-mediated immunopathology . We report here that MSRV particles Induce T-lymphocyte response with a bi as in the V beta 16 chain usage in surface receptor, whatever the HLA DR of the donor. A recombinant MSRV envelope-but not core-protein reproduced sim ilar nonconventional activation. Molecular analysis of V beta CDR3 showed t hat V beta 16 expansions are polyclonal. Our results thus provide evidence that MSRV envelope protein can trigger an abnormal immune response with sim ilar characteristics to that of superantigens. (C) 2001 Academic Press.