title: 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.
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 crossreactive. 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.
authors.affiliation: Laboratory of Immunobiology Dana-Farber Cancer Institute Harvard Medical School Boston, Massachusetts 02115.
authors.forename: R F
authors.initials: RF
authors.lastname: Siliciano
authors.forename: T
authors.initials: T
authors.lastname: Lawton
authors.forename: C
authors.initials: C
authors.lastname: Knall
authors.forename: R W
authors.initials: RW
authors.lastname: Karr
authors.forename: P
authors.initials: P
authors.lastname: Berman
authors.forename: T
authors.initials: T
authors.lastname: Gregory
authors.forename: E L
authors.initials: EL
authors.lastname: Reinherz
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000595:Amino Acid Sequence; D000943:Antigens, Differentiation; D002999:Clone Cells; D006678:HIV / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000276:immunology / Q000502:physiology*
chemical_list: D000943:Antigens, Differentiation; D014759:Viral Envelope Proteins