CD2 E-Rosette receptor, LFA-2 (lymphocyte-function antigen), T11, CD2R(refers to crytic epitopes exposed after activation), SRBC-R (sheep red blood cell), Tp50
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Lineage Restricted Molecule
Type 1 glycoprotein
T Cell
NK Cell
Thymocyte
B Cell
T Lymphocyte
Macrophage
50 / 50

Expression
CD2 is expressed on virtually all thymocytes, T lymphocytes and NK cells.  CD2 is expressed on thymic T cells, peripheral T cells and approximately 50% in thymic B cells.  The expression on mature B cells is controversial.  CD2 is expressed on mouse and porcine B cells and also on rat, ovine, and bovine splenic macrophages.

Structure
MOLECULAR FAMILY NAME:  Belongs to the immunoglobulin supergene family.\

CD2 is a single-pass type-1 351 aa glycoprotein.  It contains an 158 aa extracellular domain which contains 1 Ig-like C2-type domain and 1 Ig-like V-type domain but it lacks disulfide bonds and 3 potential N-linked glycoslation sites, a transmembrane domain and a 124 aa cytoplasmic domain which is rich in basic and proline residues that are essential for interactions with cytoplasmic signaling molecules and is highly conserved across species.  CD2 is the best-characterized member of a family of structurally related cell surface IgSF molecules which includes CD48, CD58, CD244 (2B4), CD229 (Ly-9), and CD150.  CD2 has a structural similarity and close genetic linkage to CD58.  The gene for CD58 lies 60 kDa-250 kb from the CD2 gene.  These 2 loci encoding CD2-related molecules appear to have arisen by duplication of an entire chromosomal region.  The structure of the entire extracellular portion of CD2 has been determined by X-ray diffraction.  As predicted for other members of this family, it contains a membrane-distal V domain lacking the canonical inter-b sheet disulfide linked by a somewhat flexible segment to a membrane-proximal C2 domain with an additional disulfide.  

MOLECULAR MASS
Cell Type Unreduced Reduced
Lymphocytes (T, NK) 50 kDa 50 kDa

POST-TRANSCRIPTIONAL MODIFICATION

There is no alternative splicing form.

POST-TRANSLATIONAL MODIFICATION

CD2 has 3 potential N-linked glycosylation sites in the extracellular region.  Crosslinking of TcR/CD3 upregulates CD2 avidity for its ligand CD58.

Ligands
The major ligand for the extracellular portion of human CD2 is CD58.  No CD58 orthologue has been identified in the rat or mouse.  CD48 appears to be the major ligand in these species.  Human CD2 has also been reported to bind CD48 and CD59.  CD58 and CD48 both bind to the GFCC'C" b sheet of the membrane-distal IgSF domain of CD2.  Structural and mutagenesis studies suggest that CD2 interacts with CD48 and CD58 in a head-to-head orientation with the complex predicted to span ~134 A, similar to the dimensions of a T cell receptor/peptide/MHC complex which also spans ~134 A.  CD2 binds CD58 in solution with a very low affinity of kDa 9-22 mM and dissociates rapidly with Koff >4s-1.  Membrane-attached CD58 binds half-maximally to cell surface CD2 at a surface density of ~10-20 molecules/m m and there is a rapid exchange of bound and free CD58 at the contact interface.  Immunoprecipitation studies indicate an association between CD2 and several transmembranes, T cell receptor/CD3 complex, CD5, CD45 and CD53 and cytoplasmic proteins, Lck, Fyn, phosphatidylinositol 3-kinase, and tubulin.  The interaction with Lck involves 2 of the proline-rich regions in CD2 which bind the SH3 domain of Lck.

LIGANDS AND MOLECULES ASSOCIATED WITH CD2
Molecule Comment
CD58 (LFA-3) Binds to CD2 domain 1
CD48 (Blast1) Binds to CD2 domain 1
CD59 (HRF20) Binds to CD2 domain 1
CD15 (Lewis-x) Binds to multimeric CD2
Sulfate carbohydrate Ligand
CD3-z, e chain Associates with CD2
CD16-z chain Associates with CD2
CD45 Associates with CD2
CD11a/CD18 Associates with CD2


Function
CD2 acts as an adhesion and signal-transducing molecule.  The interaction between CD2 and its ligands, CD48 and CD58 (LFA-3), enhances T cell Ag recognition and activation.  This is attributable to improved adhesion between T cells and antigen-presenting cells or target cells and signals transmitted through the CD2 cytoplasmic domain.  No abnormalities have been detected in CD2-deficient mice.  CD2 plays a critical role in alternative T cell activation, in the regulatory molecule in T- or NK-mediated cytolysis, in the induction of apoptosis in the activated peripheral T cells, in the production of cytokines by T cells and in the regulation of T cell anergy.

BIOCHEMICAL ACTIVITY

CD2 primarily binds CD58 on antigen-presentation cells and induces co-stimulatory signals in T cells.  PLC-g-1, p56-lck, p59-fyn, CD3-z and CD3e are tyrosine phosphorylated after CD2 stimulation.

DISEASE RELEVANCE AND FUNCTION OF CD2 IN INTACT ANIMALS

In vivo administration of the CD2 mAb or the CD2 ligand, CD48 induces immunosuppression.  The CD2 ligand, soluble CD58 or anti-CD2 antibody, induces sustained T cell unresponsiveness.  CD2 is an original T cell marker.  It is using in typing leukemias and lymphomas and is a therapeutic means in preventing allograft rejection.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD2

At least 6 proteins bind to the CD2 transcriptional enhancer which is located 3' to the gene.  These include elf1, a member of the ets family and sox4, a member of the HMG family of transcription factors.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD2: No information.

ADDITIONAL INSIGHTS

The ligand for CD2R, recognized by agonistic mAbs such as T11-3, 9.1 and L304, has not yet been identified.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgen 914P06729
MouseB28967P08920Y00023
RatA33071P08921X05111
Antibodies
36F-18   View Reactivity
39C1.5   View Reactivity
7C2B   View Reactivity
8-1E3   View Reactivity
B26A4   View Reactivity
BAQ95A   View Reactivity
BAT18A   View Reactivity
BAT42A   View Reactivity
BAT76A   View Reactivity
CACT31A   View Reactivity
CC42   View Reactivity
CH128A   View Reactivity
CH132A   View Reactivity
CH134A   View Reactivity
CH61A   View Reactivity
HB88A   View Reactivity
I/35A   View Reactivity
LT2   View Reactivity
MAC288   View Reactivity
MSA4   View Reactivity
MUC2A   View Reactivity
PG168A   View Reactivity
PGBL6A   View Reactivity
RPA-2.10   View Reactivity
SFCI3PtH9   View Reactivity

Revised June 25, 2008


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