CHARACTERIZATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-SPECIFIC CYTOTOXIC T-LYMPHOCYTE CLONES ISOLATED DURING ACUTE SEROCONVERSION - RECOGNITION OF AUTOLOGOUS VIRUS SEQUENCES WITHIN A CONSERVED IMMUNODOMINANTEPITOPE

Virus-specific cytotoxic T lymphocytes (CTL) are involved in protectiv e immunity to many virus infections. It has recently been shown that C TL are detectable early during primary infection with the primate lent iviruses, human immunodeficiency virus type 1 (HIV-1) and simian immun odeficiency virus. To better characterize the CTL response during acut e HIV-1 infection, HIV-1-specific CTL clones were generated from two p atients during symptomatic HIV-1 seroconversion. These CTL clones demo nstrated specificity for env of HIV-1 and recognized sequences within gp41. Two human histocompatibility leukocyte antigen (HLA) A31-restric ted clones from the same individual were found to have differing virus strain specificities. Both clones recognized the 11-amino acid peptid e RLRDLLLIVTR from position 770-780 of gp41. A change from T to V at p osition 779 in this epitope abrogated lysis by one clone but not the o ther. A CTL clone from the other patient, restricted by a different cl ass I HLA allele, recognized the nine-amino acid peptide HRLRDLLLI fro m position 769-777 of gp41, Of note, the peptide RLRDLLLIVTR has been shown by others to be presented to CTL by HLA-A3.1. Autologous virus s equences from seroconversion and up to 15 wk after presentation in the se two patients were recognized by the CTL clones-isolated during acut e infection. None of the CTL clones recognized the MN strain of HIV-1, indicating the problems inherent in relying on a single virus strain in the development of a vaccine. These studies have identified an immu nodominant and promiscuous area for the generation of CTL responses wi thin gp41. This recognition of autologous virus sequences by the initi al CTL response is consistent with the hypothesis that a single virus strain is transmitted to the seroconverter and that the CTL response i s involved in the initial control of that virus. These studies indicat e the importance of the CTL response to HIV-1 infection and have impli cations in the design of vaccines.