Analysis of host-virus interactions in AIDS with anti-gp120 T cell clones: Effect of HIV sequence variation and a mechanism for CD4+ cell depletion

Robert F Siliciano, Trebor Lawton, Cindy Knall, Robert W. Karr, Phillip Berman, Timothy Gregory, Ellis L. Reinherz

Research output: Contribution to journalArticle

Abstract

The primary human T cell response to HIV was analyzed by isolating from seronegative donors T cell clones specific for HIV gp120. T cell epitopes restricted by different MHC elements were identified within gp120, and synthetic peptides were used to address the fundamental problem of how HIV sequence variability affects T cell recognition. Even one conservative substitution can drastically reduce recognition; thus the interaction of gp120 epitopes with T cell receptors and MHC is precise and poorly cross-reactive. Importantly, a subset of CD4+ gp120-specific clones manifest cytolytic activity and lyse uninfected autologous CD4+Ia+ T cells in the presence of gp120 in a process that is strictly dependent upon CD4-mediated uptake of gp120 by T cells. Assuming gp120 is shed from HIV-infected cells in vivo, this novel CD4-dependent autocytolytic mechanism may contribute to the profound depletion of CD4+ cells in AIDS.

Original languageEnglish (US)
Pages (from-to)561-575
Number of pages15
JournalCell
Volume54
Issue number4
DOIs
StatePublished - Aug 12 1988
Externally publishedYes

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T-cells
Viruses
Acquired Immunodeficiency Syndrome
Clone Cells
HIV
T-Lymphocytes
HIV Envelope Protein gp120
T-Lymphocyte Epitopes
T-Cell Antigen Receptor
Epitopes
Substitution reactions
Thomsen-Friedenreich antibodies
Peptides

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Analysis of host-virus interactions in AIDS with anti-gp120 T cell clones : Effect of HIV sequence variation and a mechanism for CD4+ cell depletion. / Siliciano, Robert F; Lawton, Trebor; Knall, Cindy; Karr, Robert W.; Berman, Phillip; Gregory, Timothy; Reinherz, Ellis L.

In: Cell, Vol. 54, No. 4, 12.08.1988, p. 561-575.

Research output: Contribution to journalArticle

Siliciano, Robert F ; Lawton, Trebor ; Knall, Cindy ; Karr, Robert W. ; Berman, Phillip ; Gregory, Timothy ; Reinherz, Ellis L. / Analysis of host-virus interactions in AIDS with anti-gp120 T cell clones : Effect of HIV sequence variation and a mechanism for CD4+ cell depletion. In: Cell. 1988 ; Vol. 54, No. 4. pp. 561-575.
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