Document 0140
 DOCN  M95B0140
 TI    The effects of natural altered peptide ligands on the whole blood
       cytotoxic T lymphocyte response to human immunodeficiency virus.
 DT    9511
 AU    Klenerman P; Meier UC; Phillips RE; McMichael AJ; Nuffield Department of
       Clinical Medicine, John Radcliffe; Hospital, Oxford, GB.
 SO    Eur J Immunol. 1995 Jul;25(7):1927-31. Unique Identifier : AIDSLINE
       MED/95347391
 AB    Cytotoxic T lymphocytes (CTL) directed against human immunodeficiency
       virus (HIV)-1 are detectable in the majority of infected individuals,
       and their early appearance as the initial viremia is suppressed is
       thought to represent a potent antiviral response. Variation which arises
       in CTL epitopes can affect recognition by CTL, and we have observed
       previously that variant epitopes in HIV-1 gag which arise in
       HIV-1-seropositive donors may act as T cell receptor (TCR) antagonists
       of their own CTL (Klenerman et al., Nature 1994, 369: 403). The most
       important question arising from these observations is the extent of
       these immune escape mechanisms in vivo. Here we show that fresh,
       uncultured lymphocytes taken directly from HIV-1-infected patients are
       susceptible to TCR antagonism by variants present within their own
       virus. In contrast to HLA Class II-restricted T cell responses, where
       anergy may be induced, we find that in vitro, natural variants may
       stimulate and sustain growth of CTL. These CTL lines retain lytic
       specificity exclusively for the original peptide. If this represents
       events in vivo, natural HIV altered peptide ligands (APL) have the
       capacity to inhibit the range of CTL directed against an epitope, not
       simply those clones selected in vitro. Partial activation of CTL by APL
       could also act to drive an ineffectual CTL response incapable of lysing
       infected cells bearing these natural antigenic variants. Distortion of
       lymphocyte populations and function by APL might represent a further
       mechanism of immune evasion by HIV.
 DE    Amino Acid Sequence  Antigenic Determinants  Base Sequence  Case Report
       DNA Primers/CHEMISTRY  Human  HIV/*IMMUNOLOGY  Immunity, Cellular
       Ligands  Lymphocyte Transformation  Male  Molecular Sequence Data
       Peptides/CHEMISTRY/IMMUNOLOGY  Support, Non-U.S. Gov't  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).