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.
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.
Siliciano
R F
RF
Laboratory of Immunobiology Dana-Farber Cancer Institute Harvard Medical School Boston, Massachusetts 02115.
Lawton
T
T
Knall
C
C
Karr
R W
RW
Berman
P
P
Gregory
T
T
Reinherz
E L
EL
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*
D000943:Antigens, Differentiation; D014759:Viral Envelope Proteins