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M9650121.TXT
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1996-03-09
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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).