       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).

