parking..... I've done a lot of work with paired anti-T11(2) and anti-T11(3). That was the reason for my original fascination with CD2........
J Biol Chem 2001 Jun 1;276(22):18775-85
Dynamic Recruitment of Human CD2 into Lipid Rafts. LINKAGE TO T
CELL SIGNAL TRANSDUCTION.
Yang H, Reinherz EL.
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-T11(2) + anti-T11(3)) 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. |
