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J. Biol. Chem., Vol. 276, Issue 22, 18775-18785, June 1, 2001
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From the Laboratory of Immunobiology, Dana-Farber Cancer Institute
and the Department of Medicine, Harvard Medical School,
Boston, Massachusetts 02115
CD2 mediates T cell adhesion via its
ectodomain and signal transduction utilizing its 117-amino acid
cytoplasmic tail. Here we show that a significant fraction of human CD2
molecules is inducibly recruited into lipid rafts upon CD2
cross-linking by a specific pair of mitogenic anti-CD2 monoclonal
antibodies (anti-T112 + anti-T113) or
during cellular conjugate formation by CD58, the physiologic ligand
expressed on antigen-presenting cells. Translocation to lipid
microdomains is independent of the T cell receptor (TCR) and, unlike
inducible TCR-raft association, requires no tyrosine phosphorylation. Structural integrity of rafts is necessary for CD2-stimulated elevation of intracellular free calcium and tyrosine phosphorylation of cellular substrates. Whereas murine CD2 contains two
membrane-proximal intracellular cysteines, partitioning CD2 into
cholesterol-rich lipid rafts constitutively, human CD2 has no
cytoplasmic cysteines. Mapping studies using CD2 point mutation, deletion, and chimeric molecules suggest that conformational change in
the CD2 ectodomain participates in inducible raft association and
excludes the membrane-proximal N-linked glycans, the
transmembrane segment, and the CD2 cytoplasmic region (residues 8-117)
as necessary for translocation. Translocation of CD2 into lipid
rafts may reorganize the membrane into an activation-ready state
prior to TCR engagement by a peptide associated with a major
histocompatibility complex molecule, accounting for synergistic T cell
stimulation by CD2 and the TCR.
Dynamic Recruitment of Human CD2 into Lipid Rafts
LINKAGE TO T CELL SIGNAL TRANSDUCTION*
*
This work was supported by National Institutes of Health
Grant AI21226.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Lab. of Immunobiology,
Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115. Tel.:
617-632-3412; Fax: 617-632-3351; E-mail: ellis_reinherz@ dfci.harvard.edu.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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