Elicitation and specificity of anti-vesicular stomatitis virus-specific cytotoxic T lymphocytes.

Abstract

We have examined the major histocompatibility complex (MHC) control and antigen specificity of 2 antiviral effector mechanisms elicited during infection of mice with vesicular stomatitis virus (VSV). Infection of mice with VSV results in the elicitation of anti-VSV cytotoxic T lymphocytes (CTL) that are functionally restricted to virus-infected targets which are syngeneic at the H-2K and H-2D ends of the MHC. The ability to generate high levels of anti-VSV CTL activity was found to be controlled by the H-2 haplotype of the responding mouse. Mice with either H-2(d) or H-2(b) haplotypes were found to be high responders to VSV infection, while mice of the H-2(k) haplotype were low responders. The observed difference in the ability to generate anti-VSV CTL by the various strains could not be attributed to artifactual differences in the susceptibility to lysis of the syngeneic targets but was a true reflection of immune responsiveness to VSV infection, which mapped to the H-2K IA and/or H-2D ends of the MHC. The anti-VSV antibody response or the natural killer response induced by VSV infection, on the other hand, did not appear to be controlled by the MHC. The specificities of the anti-VSV CTL and of the antibodies elicited as a result of infection were also examined. It was found that 2 serologically distinct strains of VSV (Indiana and New Jersey) elicit CTL that lyse target cells infected with the heterologous virus serotype. Studies to evaluate the target antigen of this cross-reactive lysis indicated that expression of the major surface glycoprotein (G protein) was needed for recognition by cross-reactive anti-VSV CTL. In summary, the observation that the CTL and B cell responses to VSV infection differ both with respect to specificity and MHC-controlled responsiveness suggests that the host can interact with, process, and present viral antigens in different ways, depending on the effector mechanism involved.