Herpes simplex virus-specific cytolytic T lymphocytes restricted to a normally low responder H-2 allele are protective in vivo.

The herpes simplex virus (HSV)-specific cytolytic T lymphocyte (CTL) response in C57BL/6 (B6, H-2b) mice is restricted exclusively to the class I major histocompatibility complex (MHC) glycoprotein H-2Kb, with no detectable response restricted by H-2Db. However, analysis of the memory CTL population derived from B10.A(2R) (Kk Db) mice indicated that Db was a functional restriction element, and that failure to detect this subpopulation in B6 mice was not caused by the inability of HSV-derived antigens to associate with this self protein. Two long-term polyclonal CTL lines, one generated from B6 mice restricted by Kb and a second generated from 2R mice restricted by Db, were greater than 99% CD8+ and exhibited no natural killer (NK) cell activity. The adoptive transfer of either CTL line to naive recipients prior to infection in the hind footpads with HSV resulted in reduced levels of virus recovered from footpad tissue during the acute phase of infection and a reduction in latent HSV able to be reactivated from the sensory dorsal root ganglia (DRG) during the latent phase of infection. These results demonstrated not only that HSV antigen(s) may associate with Db, allowing restricted recognition controlled by this H-2 gene product, but also that functional Db-restricted CTL have the potential to exert biological activity in an environment in which they are not normally generated.