Ligand-induced conformational change within the CD2 ectodomain accompanies receptor clustering: implication for molecular lattice formation.
CD2 mediates interaction between T cells and their cognate partners through its CD58-binding membrane-distal adhesion domain (D1) facilitating T cell receptor (TCR) triggering. A neoepitope defined by anti-CD2R monoclonal antibodies (mAbs) has suggested structural alteration within the CD2 ectodomain during T cell activation. Here, we map CD2R to the flexible CD2 linker region between D1 and the membrane-proximal extracellular domain (D2) and show that exposure of this conformational site is independent of temperature and metabolic energy. Co-ligation of CD2 and CD58 molecules on opposing cells within a conjugate pair induces CD2R and redistributes CD2 to the region of cell-cell contact. These CD2R+ molecules, in contrast to the CD2R-molecules, are tightly clustered on the T cell surface. Hence, a ligand-mediated increase in the D1-D2 interdomain angle apparently exposes CD2R, facilitates packing of CD2 molecules in a clustered array and is linked to CD2-mediated adhesion and activation events. Conformational alteration of this type may be generally important in ordered lattice formation involving surface receptors.
Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA, USA.
J
J
Li
A
A
Smolyar
R
R
Sunder-Plassmann
E L
EL
Reinherz
D018801:CD2 Antigens / Q000276:immunology / Q000378:metabolism*; D002448:Cell Adhesion; D002460:Cell Line; D018604:Epitope Mapping; D006801:Humans; D008024:Ligands; D009154:Mutation; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology
D018801:CD2 Antigens; D008024:Ligands; D011971:Receptors, Immunologic