RECOGNITION OF HERPES-SIMPLEX VIRUS TYPE-2 TEGUMENT PROTEINS BY CD4 T-CELLS INFILTRATING HUMAN GENITAL HERPES LESIONS

The local cellular immune response to herpes simplex virus (HSV is imp ortant in the control of recurrent HSV infection. The antiviral functi ons of infiltrating CD4-bearing T cells may include cytotoxicity, inhi bition of viral growth, lymphokine secretion, and support of humoral a nd CD8 responses. The antigens recognized by many HSV-specific CD4 T c ells localizing to genital HSV-2 lesions are unknown. T cells recogniz ing antigens encoded within map units 0.67 to 0.73 of HSV DNA are freq uently recovered from herpetic lesions. Expression cloning with this r egion of DNA now shows that tegument protein VP22 and the viral dUTPas e, encoded by genes U(L)49 and U(L)50, respectively, are T-cell antige ns. Separate epitopes in VP22 were defined for T-cell clones from each of three patients. Reactivity with the tegument protein encoded by U( L)21 was identified for an additional patient. Three new epitopes were identified in VP16, a tegument protein associated with VP22, Some teg ument-specific CD4 T-cell clones exhibited cytotoxic activity against HSV-infected cells. These results suggest that herpes simplex tegument proteins are processed for antigen presentation in vivo and are possi ble candidate compounds for herpes simplex vaccines.