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Dynamic interactions between CD4 and α4β7 on primary CD4+ T cells indicate a novel coupling of these two costimulatory receptors

Friday, November 08, 2013 — Poster Session IV

2:00 p.m. – 4:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • J. Hiatt
  • D. Van Ryk
  • N. Patel
  • F. Nawaz
  • C. Schwing
  • S. Ganesan
  • N.C. Okwara
  • D. Wei
  • C. Cicala
  • A. Fauci
  • J. Arthos


Cell-to-cell spread of HIV is facilitated by transmission across virological synapses, adhesive junctions that protect virions from antibodies while promoting viral entry. These synapses, like immunological synapses, are dependent upon interactions between ICAM and integrin LFA-1 in the high-affinity “active” conformation. LFA-1 can be activated by signaling through integrin α4β7. The HIV envelope protein gp120 binds to and signals through α4β7, which rapidly activates LFA-1. Using confocal microscopy and fluorescence lifetime imaging (FLIM) detection of FRET, we find that the LFA-1, CD4 and α4β7 form a complex on the surface of primary CD4+ T cells. Both CD4 and α4β7 function as costimulatory molecules in the context of antigen-specific CD4+ T cell responses. However they are not known to function in a coordinated way. We find that both CD4 and α4β7 are closely associated on the cell surface (< 10nM). The degree of colocalization varies between cellular subsets and can be modulated by treating cells with gp120, which also inversely modulates CD4-LFA-1 association. The specific interaction between CD4 and α4β7 suggests a novel functional coupling of these two costimulatory receptors. HIV likely utilizes α4β7 by taking advantage of the normal cellular processes in which these two receptors work together.

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