Document 0899 DOCN M9440899 TI Characterization of human immunodeficiency virus type 1-specific cytotoxic T lymphocyte clones isolated during acute seroconversion: recognition of autologous virus sequences within a conserved immunodominant epitope. DT 9404 AU Safrit JT; Andrews CA; Zhu T; Ho DD; Koup RA; Aaron Diamond AIDS Research Center, New York University School of; Medicine, New York 10016. SO J Exp Med. 1994 Feb 1;179(2):463-72. Unique Identifier : AIDSLINE MED/94125027 AB Virus-specific cytotoxic T lymphocytes (CTL) are involved in protective immunity to many virus infections. It has recently been shown that CTL are detectable early during primary infection with the primate lentiviruses, human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus. To better characterize the CTL response during acute HIV-1 infection, HIV-1-specific CTL clones were generated from two patients during symptomatic HIV-1 seroconversion. These CTL clones demonstrated specificity for env of HIV-1 and recognized sequences within gp41. Two human histocompatibility leukocyte antigen (HLA) A31-restricted clones from the same individual were found to have differing virus strain specificities. Both clones recognized the 11-amino acid peptide RLRDLLLIVTR from position 770-780 of gp41. A change from T to V at position 779 in this epitope abrogated lysis by one clone but not the other. A CTL clone from the other patient, restricted by a different class I HLA allele, recognized the nine-amino acid peptide HRLRDLLLI from 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 sequences from seroconversion and up to 15 wk after presentation in these two patients were recognized by the CTL clones isolated during acute 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 immunodominant and promiscuous area for the generation of CTL responses within gp41. This recognition of autologous virus sequences by the initial CTL response is consistent with the hypothesis that a single virus strain is transmitted to the seroconverter and that the CTL response is involved in the initial control of that virus. These studies indicate the importance of the CTL response to HIV-1 infection and have implications in the design of vaccines. DE Adult Amino Acid Sequence Base Sequence Cell Line, Transformed Clone Cells Conserved Sequence DNA Female Gene Products, env/IMMUNOLOGY Human HIV Seropositivity/*IMMUNOLOGY HIV-1/*IMMUNOLOGY Immunodominant Epitopes/*IMMUNOLOGY Male Molecular Sequence Data Support, Non-U.S. Gov't Support, U.S. Gov't, P.H.S. T-Lymphocytes, Cytotoxic/*IMMUNOLOGY JOURNAL ARTICLE SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).