ANTIGENIC SPECIFICITIES OF HUMAN CD4(+) T-CELL CLONES RECOVERED FROM RECURRENT GENITAL HERPES-SIMPLEX VIRUS TYPE-2 LESIONS

Lesions resulting from recurrent genital herpes simplex virus (HSV) infection are characterized by infiltration of CD4(+) lymphocytes. We have investigated the antigenic specificity of 47 HSV-specific CD4(+) T-cell clones recovered from the HSV-2 buttock and thigh lesions of five patients. Clones with proliferative responses to recombinant truncated glycoprotein B (gB) or go of HSV-2 or purified natural gC of HSV-2 comprised a minority of the total number of HSV-specific clones isolated from lesions. The gC2- and gD2-specific CD4(+) clones had cytotoxic activity. The approximate locations of the HSV-2 genes encoding HSV-2 type-specific CD4(+) antigens have been determined by using HSV-1 x HSV-2 intertypic recombinant virus and include the approximate map regions 0.30 to 0.46, 0.59 to 0.67, 0.67 to 0.73, and 0.82 to 1.0 map units. The antigenic specificity of an HLA DQ2-restricted, HSV-2 type-specific T-cell clone was mapped to amino acids 425 to 444 of V16 of HSV-2 by sequential use of an intertypic recombinant virus containing VP16 of HSV-2 in an HSV-1 background, recombinant VP16 fusion proteins, and synthetic peptides. Each of the remaining four patients also yielded at least one type-specific T-cell clone reactive with an HSV-2 epitope mapping to approximately 0.67 to 0.73 map units. The antigenic specificities of lesion-derived CD4(+) T-cell clones are quite diverse and include at least 10 epitopes. Human T-cell clones reactive with gC and VP16 are reported here for the first time.