CD58 LFA-3(lymphocyte function-associated antigen-3)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
Type 1 glycoprotein
Hematopoietic Cell
Nonhematopoietic Cell
Erythrocyte
Fibroblast
Endothelial Cell
Epithelia
Germinal Center
Thymocyte
Blood Cell
Dendritic Cell
Macrophage
Monocyte
T Cell
B Cell
Peripheral blood
Leukocyte
Muscle, Smooth
40 / 40
70 / 70

Expression
CD58 is expressed in many tissues such as most hematopoietic cells, erythrocytes, and on various non-hematopoietic cells, such as leukocytes, fibroblasts, endothelial, smooth muscle and epithelia.  It is expressed on about half of peripheral blood B and T cells and at high levels on monocytes.  Expression is particularly high on memory T cells and dendritic cells.  In lymphoid tissues CD58 is expressed on all dendritic cells and macrophages, and on germinal center B cells, medullary thymocytes and medullary, but not cortical, thymic epithelial cells.  The sheep CD58 orthologue binds human CD2 and mediates the phenomenon of sheep erythrocyte rosetting on human T cells.



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

CD58 is a single-pass type-1 integral glycoprotein.  It contains an 188 extracellular domain which contains an Ig-like C2-type domain having a disulphide bond, an Ig-like V-type domain which does not have a disulphide bond and 6 potential N-glycosylation sites and a 12 aa cytoplasmic domain.  The integral transmembrane glycoprotein and GPI-anchored form occurs on all cells except erythrocytes which are only expressed on the GPI-linked form.  CD58 is a member of the CD2 family of molecules, which includes CD48 and CD150.  Within this group CD58 is most similar to CD48, which is the major CD2 ligand in the mouse and rat.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
JY 55-70 kDa
Erythrocyte 40-70 kDa

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 2 different isoforms, the transmembrane anchored form and GPI-anchored form.

POST-TRANSLATIONAL MODIFICATION

There are 6 potential N-glycosylation sites are in the extracellular domain.


Ligands
The extracellular portion of CD58 binds to CD2 on the GFCC'C'' b  sheet of the V-set domain.  CD2 binds CD58 in solution with a very low affinity of kDa 9-22 mM as a result of a very fast dissociation rate constant, K off > 4 s-1. Membrane-attached GPI-anchored CD58 binds half-maximally to the cell surface CD2 at a surface density of ~20 molecules/mM and there is a rapid exchange of bound and free CD58 at the adhesion interface.

LIGANDS AND MOLECULES ASSOCIATED WITH CD58
Molecule Comment
CD2 CD2 is the only known receptor for CD58




Function
CD58 mediates adhesion between killer and target cells, antigen presenting cells, T cells, thymocytes and thymic epithelial cells.  CD58 provides a co-stimulatory signal in immune response and activation of killer cells.  CD58 is expressed on antigen-presenting cells and enhances T cell antigen recognition through binding to CD2.  CD58 is a ligand for CD2 providing a costimulatory signal on immune responses.  CD58/CD2 binding mediates adhesion between killer and target cells and thus plays a role in cell-mediated cytotoxicity.  Adhesion via CD2 occurs between APC and T cells as well as between thymocytes and thymic epithelial cells and in T-cell-erythrocyte interaction.  The CD2/CD58 interaction may prime cellular responses by both the CD2-positive and the CD58-positive cells as both forms of CD58 have singaling activity.  This is partly a consequence of improved adhesion but signals transmitted through CD2 may also contribute.  Structural studies suggest that the CD2-mediated adhesion may optimize the inter-membrane distance for antigen recognition by the T cell receptor.  CD58 antibodies can inhibit CD2/CD58 interactions.

BIOCHEMICAL ACTIVITY

CD58 is a ligand for CD2.

DISEASE RELEVANCE AND FUNCTION OF CD58 IN INTACT ANIMAL

CD58 is absent from erythrocytes of patients with paroxysmal nocturnal hemoglobinuria.

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD58: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD58: No information.


Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene 965P19256
Antibodies
1C3   View Reactivity
L180/1   View Reactivity
RTH32A   View Reactivity
RTH33A   View Reactivity

Revised June 25, 2008


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