The role of vesicular stomatitis virus major glycoprotein in determining the specificity of virus-specific and H-2-restricted cytolytic T cells.

Abstract

AbstractPossible involvement of the major glycoprotein (G protein) of vesicular stomatitis virus (VSV), which is expressed on infected cell surfaces, in the virus‐specific and H‐2‐restricted lysis of targets by cytotoxic T lymphocytes (CTL) was sought by examining the effect of monoclonal antibody directed against the G protein of Indiana (VSVInd) or New Jersey (VSVNJ) serotypes. Evidence is presented that hybridoma supernatants containing monoclonal antibody of the IgG class directed against the G protein of VSVNJ could specifically block the lytic activity of primary CTL obtained from BALB/c mice infected with UV‐inactivated VSVNJ, but not VSVInd for homotypic but not heterotypic VSV‐infected P815 Y cells. Likewise, monoclonal anti‐VSVIndand anti‐G protein antibody proved effective in blocking the lysis mediated by VSVInd‐ but not VSVNJ‐primed CTL against targets infected with VSVInd, but not those infected with VSVNj. The results of blocking assays are consistent with the interpretation that UV‐inactivated VSVNJ or VSVInd could generate, during the primary in vivo response, CTL subsets which were able to distinguish between serologically distinct VSV G proteins and those which were cross‐reactive for both serotypes. Purified G protein derived from either of the 2 VSV serotypes could in in vitro culture trigger the generation of completely serotype‐specific and H‐2‐restricted secondary CTL from nonlytic precursors primed in vivo with homologous VSV serotype. The lytic activity of secondary VSVNJ‐ and VSVInd‐specific CTL could be blocked by incubation of infected targets with monoclonal anti‐VSVNJ and anti‐VSVInd G protein antibodies, respectively. The data obtained are taken as suggestive evidence for the specific recognition of VSV G protein expressed on target cells by virus‐specific CTL.