The cytotoxic T-cell response to herpes simplex virus type 1 infection of C57BL/6 mice is almost entirely directed against a single immunodominant determinant

Many virus infections give rise to surprisingly limited T-cell responses di rected to very few immunodominant determinants. We have been examining the cytotoxic T-lymphocyte (CTL) response to herpes simplex virus type 1 (HSV-1 ) infection. Previous studies have identified the glycoprotein E-derived pe ptide from residues 498 to 505 (gB(498-505)) as one of at least three deter minants recognized by HSV-1-specific CTLs isolated from C57BL/6 mice. We ha d previously found that in vitro-derived CTLs directed to gB(498-505) show a characteristic pattern of T-cell receptor (TCR) usage, with 60% of gB(498 -505)-specific CD8(+) T cells expressing BV10(+) TCR beta chains and a furt her 20% expressing BV8S1. In this report, we confirm that this TCR V-region bias is also reflected in the ex vivo response to HSV-1 infection. A high proportion of activated CD8(+) draining lymph node cells were found to expr ess these dominant V regions, suggesting that a substantial number of in vi vo responding T cells were directed to this one viral determinant. The use of an HSV-1 deletion mutant lacking the gB(498-505) determinant in combinat ion with accurate intracellular gamma interferon staining allowed us to qua ntify the extent of gB-specific T-cell dominance. Together, these results s uggested that between 70 and 90% of all CD8(+) HSV-1-specific T cells targe t gB(498-505). While deletion of this determinant resulted in an attenuated CD8(+) T-cell response, it also permitted the emergence of one or more pre viously unidentified cryptic specificities. Overall, HSV-1 infection of C57 BL/6 mice results in am extremely focused pattern of CD8(+) T-cell selectio n in terms of target specificity and TCR expression.