Document 0042
 DOCN  M9470042
 TI    Cytotoxic T-cell activity antagonized by naturally occurring HIV-1 Gag
       variants [see comments]
 DT    9409
 AU    Klenerman P; Rowland-Jones S; McAdam S; Edwards J; Daenke S; Lalloo D;
       Koppe B; Rosenberg W; Boyd D; Edwards A; et al; Nuffield Department of
       Clinical Medicine, University of Oxford,; UK.
 SO    Nature. 1994 Jun 2;369(6479):403-7. Unique Identifier : AIDSLINE
       MED/94255016
 CM    Comment in: Nature 1994 Jun 2;369(6479):355
 AB    Most asymptomatic individuals infected with HIV-1 have a cytotoxic T
       lymphocyte (CTL) response to the virus Gag proteins which can be
       demonstrated in vitro. Epitopes have been mapped in p17 Gag and p24 Gag
       restricted by HLA-B8 (p17-3 and p24-13) and B27 (p24-14). Viruses
       isolated from patients who make CTL responses to these peptides vary
       within the genetic sequences encoding these epitopes and some mutations
       lead to reduction in killing activity in vitro. This was attributed to
       either failure of the variant epitope to bind major histocompatibility
       complex class I or failure of T-cell receptors to bind the presented
       peptide. But peptide variants of class I-restricted epitopes cause
       'antagonism', that is, the presence of a variant epitope (in the form of
       peptide) inhibits normal lysis of targets presenting the original
       epitope. This mirrors similar findings in class II-restricted systems.
       Here we report that naturally occurring variant forms of p17-3, p24-13
       and p24-14 may cause antagonism of CTL lines derived from the same
       individuals. The effect is present if the epitopes are derived from
       synthetic peptides and when they are processed from full-length proteins
       expressed by either recombinant vaccinia constructs or replicating HIV.
 DE    Amino Acid Sequence  Antigenic Determinants/GENETICS/IMMUNOLOGY  Cell
       Line  Gene Products, gag/GENETICS/*IMMUNOLOGY  Human  HIV
       Antigens/GENETICS/IMMUNOLOGY  HIV Core Protein p24/GENETICS/IMMUNOLOGY
       HIV-1/*IMMUNOLOGY  HLA-B8 Antigen/IMMUNOLOGY  Molecular Sequence Data
       Peptide Fragments/CHEMICAL SYNTHESIS/GENETICS/IMMUNOLOGY  Receptors,
       Antigen, T-Cell/*ANTAGONISTS & INHIB/IMMUNOLOGY  Recombinant
       Proteins/GENETICS/IMMUNOLOGY  Support, Non-U.S. Gov't  T-Lymphocytes,
       Cytotoxic/*IMMUNOLOGY  Vaccinia Virus/GENETICS  Variation (Genetics)
       JOURNAL ARTICLE

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