Document 0121
 DOCN  M9650121
 TI    Recognition of the highly conserved YMDD region in the human
       immunodeficiency virus type 1 reverse transcriptase by HLA-A2-restricted
       cytotoxic T lymphocytes from an asymptomatic long-term nonprogressor.
 DT    9605
 AU    Harrer E; Harrer T; Barbosa P; Feinberg M; Johnson RP; Buchbinder S;
       Walker BD; AIDS Research Center and Infectious Disease Unit,
       Massachusetts; General Hospital, Boston 02114, USA.
 SO    J Infect Dis. 1996 Feb;173(2):476-9. Unique Identifier : AIDSLINE
       MED/96162113
 AB    The human immunodeficiency virus (HIV) type 1 reverse transcriptase (RT)
       is an important target for therapeutic intervention and for
       HIV-1-specific cytotoxic T lymphocytes (CTL). An HLA-A2-restricted CTL
       epitope containing the sequence YMDD, which is highly conserved among
       human and animal retroviruses and essential for function of the
       RNA-dependent DNA polymerase, is identified. The drug resistance
       mutation at RT amino acid 184 (M184V), associated with
       (-)-2'-deoxy-3'-thiacytidine (lamivudine),
       (-)-2'-deoxy-5-fluoro-3'-thiacytidine (FTC), and dideoxyinosine
       resistance, is located within this epitope and abolishes recognition by
       an established CTL response. This study demonstrates that the CTL
       response may target functionally relevant regions of the RT protein and
       suggests drug therapy may select for viral variants with altered
       susceptibility to established cellular immune responses.
 DE    Amino Acid Sequence  Antiviral Agents/PHARMACOLOGY  Base Sequence
       Conserved Sequence  Deoxycytidine/ANALOGS & DERIVATIVES/PHARMACOLOGY
       Didanosine/PHARMACOLOGY  Drug Resistance, Microbial  DNA
       Primers/CHEMISTRY  Epitopes/IMMUNOLOGY  Human  HIV
       Infections/*IMMUNOLOGY/PHYSIOPATHOLOGY  HIV-1/ENZYMOLOGY/*IMMUNOLOGY
       HLA-A2 Antigen/*IMMUNOLOGY  Molecular Sequence Data
       Oligopeptides/CHEMISTRY/IMMUNOLOGY  Polymerase Chain Reaction
       RNA-Directed DNA Polymerase/CHEMISTRY/DRUG EFFECTS/*IMMUNOLOGY  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  T-Lymphocytes,
       Cytotoxic/*IMMUNOLOGY  Zalcitabine/ANALOGS & DERIVATIVES/PHARMACOLOGY
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).