CD52 CAMPATH-1, HES, CDw52
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
GPI anchor
Lymphocyte
Monocyte
Thymocyte
Epithelial Cell
Macrophage
Peripheral blood
Dendritic Cell
Eosinophil
25 / 25
29 / 29

Expression
CD52 is typically expressed at high levels on thymocytes, lymphocytes, monocytes, and macrophages.  Expression is on peripheral blood dendritic cells and eosinophils.  CD52 is expressed, at variable levels, on the majority of lymphoid malignancies, on epithelial cells lining the male reproductive tract, which shed into seminal plasma and are acquired by spermatozoa.  But CD52 is lacking in cells which have a somatic defect in the synthesis of glycosylphosphatidylinositol GPI-anchors like lymphocytes from patients with paroxysmal nocturnal hemoglobinuria (PNH).


Structure
MOLECULAR FAMILY NAME:  Belongs to the CD24 and heat stable antigen family (HSA).

CD52 is a single-pass GPI-anchored 37 aa glycoprotein.  The cDNA encodes a 24 aa leader sequence followed by a 12 aa N-terminal sequence and a C-terminal GPI signal sequence.  The major component of this complex carbohydrate molecule is a large sialylated, polylactosamine-containing core-fucosylated tetra-antennary N-linked oligosaccharide.  CD52 has 2 subclasses which have been identified, CD52-I and CD52-II, differing only in the PI moiety of the GPI-anchor.  The functional relevance of the 2 classes is not known.  The N-terminus and GPI-anchor attachment site have been determined biochemically.  CD52 species orthologues have been identified in the monkey, dog, rat and mouse.  Although these molecules share little aa sequence homology within the short peptide core, significant sequence identities are apparent in the leader and GPI signal sequences.  Where tissue expression data are available, the expression patterns of the CD52 species homologues are similar to that of the human.  Moreover, the similarities in gene structure and promoter sequence of human CD52 and the predicted mouse homologue, B7(2), strongly support their classification as species orthologues.

MOLECULAR MASS
Cell Type Unreduced Reduced Comment
Human lymphocytes 25-29 kDa 25-29 kDa
Human spermatozoa 25-29 kDa

Mr is the apparent molecular mass of SDS gel electrophoresis.  The molecule is actually much smaller, approximately 8 kDa-9 kDa as confirmed by the total structure analysis and mass spectrometry.

POST-TRANSCRIPTIONAL MODIFICATION

The CD52 gene has 2 exons separated by 1 intron close to the signal peptide cleavage site.  There are no known alternate splice sites.  It has a novel promoter, but little is known about regulation of gene expression or message stability.

POST-TRANSLATIONAL MODIFICATION

CD52 is attached to Asn-3 which is a complex carbohydrate consisting of sialyated polylactosamine units attached to a tetra-antennary fucosylated mannose core.  At the C-terminus the peptide is attached to a glycosylphosphatidylinositol GPI-anchor which has a conventional structure similar to other mammalian GPI-anchors.  A conventional N-terminal signal peptide is removed during biosynthesis as the antigen is directed to the cell membrane.

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD52: No information.



Function
CD52 is a good target for cell lysis in vitro and in vivo but how or why is unknown.  Upon cross-linking and in the presence of appropriate costimulatory factors, antibodies induce proliferation and lymphokine production in T cells. 

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD52 IN INTACT ANIMAL

CD52 antibodies appear to be useful for lysis of target cells for complement-mediated cell lysis and antibody-mediated cellular cytotoxicity.  CD52 negative cells (in patients treated with anti-CD52 antibodies) appear to function normally.  Certain isotypes such as rat IgG2b CAMPATH-1G and human IgG1 and CAMPATH-1H are able to give long-term depletion of lymphocytes in vivo and are widely used in clinical trials for treatment of rheumatoid arthritis and lymphoid malignancies, especially CLL.  CD52 is used to treat lymphoproliferative disorders as well as to reduce lymphocyte numbers and function in autoimmune diseases and organ or bone marrow transplantation.  CD52 may be such a good target for serotherapy because the CAMPATH-1 epitope lies close to the plasma membrane, within the C-terminal tripeptide and the GPI-anchor, thus facilitating complement lysis.
        

Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD52: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD52: No information.

ADDITIONAL INSIGHTS

Cell-cell transfer of GPI-anchored molecules like CD52 may be a phenomenon of more general physiological importance.  Lymphocyte depletion with CAMPATH-1 antibodies is a useful therapeutic maneuver of proven clinical benefit which may also help to give insight into causes of disease and the role of GPI-anchored antigens.  There is no official name for the family of the very small GPI-anchored glycoproteins to which CD52 belongs.  This "family" includes the human CD24 antigen and its orthologue, the mouse heat-stable antigen or J11d.  CD52 may be used to differentiate eosinophils from neutrophils due to the strong and selective labeling of eosinophilic granulocytes.

Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
DogS77412
HumanEntrezgene 1043P31358
MonkeyS27152P32763X67495
MouseM55561
RatS40081X76697
Antibodies
YTH34.5   View Reactivity
YTH66.9HL   View Reactivity

Revised June 25, 2008


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