The Proportion of Herpes Simplex Virus-Specific Cytotoxic T Lymphocytes (Tc) That Recognize Glycoprotein C Varies between Individual Mice and Is Dependent on the Form of Immunization

In mice the immune response to HSV-1 includes a brisk Tc response that is intimately associated with the control of infection. This report evaluated the Tc response to gC, one of the envelope glycoproteins of HSV-1. This protein was recognized as a target antigen for Tc from HSV-1 immune mice only if they expressed the H-2K^b MHC allele. However, even within these "responder" strains of mice the proportion of gC specific Tc was highly variable. The failure of HSV-induced Tc to recognize gC in the context of other class 1 MHC haplotypes (H-2^d and H-2^k) was demonstrable at the clonal level and could not be attributed to peculiarities of the recombinant constructs. Surprisingly, despite the inability of H-2^k-restricted, HSV-1-induced Tc to recognize gC, when a vaccinia gC virus construct was used to immunize H-2^k strains of mice it showed a variable ability to induce memory Tc populations capable of lysing HSV-1-infected autologous cells. Of added importance was the correlation of this induced Tc response with optimum protection against subsequent challenge with HSV-1. This demonstrated that despite the presence of suitable epitopes, the context of the immunogen would also influence its ability to induce Tc. Consequently, the potential repertoire of available HSV-1-specific Tc specificities is larger than indicated by studying animals immunized with HSV.