MAJOR LINKS FOR CD52  

• NCBI LocusLink Record: 1043
• Mendelian Inheritance in Man (OMIM): 114280
• SwissProt annotated protein record: P31358

CELLULAR FUNCTION OF CD52   - No information

DISEASE RELEVANCE OF CD52 AND FUNCTION OF CD52 IN INTACT ANIMAL  

• CD52 antibodies are remarkably lytic for target cells, both with human complement and by ADCC
• Certain isotypes (e.g. rat IgG2b, CAMPATH-1G, human IgG1, CAMPATH-1H) are able to give long-term depletion of lymphocytes in vivo and are widely used in clinical trials for treatment of lymphoid malignancies (especially CLL) and as immunosuppressants (in transplantation and autoimmune disease)

• Families in which CD52 is a member
  • CD52-->CD24/HSA/CD52

MOLECULAR STRUCTURE OF CD52  

• The mature CD52 antigen has a very short peptide sequence: GQNDTSQTSSPS
• It is derived from a longer precursor by cleavage of an N-linked signal peptide and displacement of a C-linked peptide with a GPI anchor

MOLECULAR MASS OF CD52  

• Please note: MW above is the apparent molecular mass by SDS gel electrophoresis. The molecule is actually much smaller, approximately 8-9 kDa (confirmed by total structure analysis and mass spectrometry)

POST-TRANSCRIPTIONAL MODIFICATION OF CD52  

• The CD52 gene has two exons separated by an 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 OF CD52  

• Attached to Asn-3 is a complex carbohydrate consisting of sialylated 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

SUBSTRATES FOR CD52   - No information

ENZYMES WHICH MODIFY CD52   - No information

LIGANDS FOR CD52 AND MOLECULES ASSOCIATED WITH CD52   - No information

• Typically expressed at high levels on thymocytes, lymphocytes, monocytes, and macrophages
• Expressed, at variable levels, on the majority of lymphoid malignancies
• Expressed on epithelial cells lining the male reproductive tract, shed into seminal plasma and acquired by spermatozoa
• Lacking in cells which have a somatic defect in the synthesis of glycosyl phosphatidylinositol (GPI) anchors (e.g. lymphocytes from patients with PNH)

• Cell-cell transfer of GPI-linked 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-linked antigens
• No official name for the family of very small GPI-anchored glycoproteins to which CD52 belongs. This "family" includes the human CD24 antigen and its homologue, 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 **

SELECTION OF OTHER CD52-SPECIFIC REFERENCE MAB  

REVIEWS

1. Hale G,Phillips JM Clinical trials with CAMPATH-I and other monoclonal antibodies. Biochem Soc Trans 1995 23:1057 PubMed

2. Hale G,Waldmann H CAMPATH-1 monoclonal antibodies in bone marrow transplantation. J Hematother 1994 3:15 PubMed

3. Hale G,Xia MQ,Tighe HP,Dyer MJ,Waldmann H The CAMPATH-1 antigen (CDw52). Tissue Antigens 1990 35:118 PubMed

4. Kirchhoff C,Hale G Cell-to-cell transfer of glycosylphosphatidylinositol-anchored membrane proteins during sperm maturation. Mol Hum Reprod 1996 2:177 PubMed

PRIMARY CITATIONS

5. Hale G,Rye PD,Warford A,Lauder I,Brito-Babapulle A The glycosylphosphatidylinositol-anchored lymphocyte antigen CDw52 is associated with the epididymal maturation of human spermatozoa. J Reprod Immunol 1993 23:189 PubMed

6. Kirchhoff, C. Krull, N., Pera, I., and Ivell, R. 1992. Mol. Repr. Dev. 34:11-15.

7. Riechmann L,Clark M,Waldmann H,Winter G Reshaping human antibodies for therapy. Nature 1988 332:323 PubMed

8. Treumann A,Lifely MR,Schneider P,Ferguson MA Primary structure of CD52. J Biol Chem 1995 270:6088 PubMed

9. Valentin H,Gelin C,Coulombel L,Zoccola D,Morizet J,Bernard A The distribution of the CDW52 molecule on blood cells and characterization of its involvement in T cell activation. Transplantation 1992 54:97 PubMed

10. Xia MQ,Hale G,Lifely MR,Ferguson MA,Campbell D,Packman L,Waldmann H Structure of the CAMPATH-1 antigen, a glycosylphosphatidylinositol- anchored glycoprotein which is an exceptionally good target for complement lysis. Biochem J 1993 293:633 PubMed

11. Xia MQ,Tone M,Packman L,Hale G,Waldmann H Characterization of the CAMPATH-1 (CDw52) antigen: biochemical analysis and cDNA cloning reveal an unusually small peptide backbone. Eur J Immunol 1991 21:1677 PubMed

WWW RESOURCES

Portions copyright by Garland Press and by the International Workshops on Human Leukocyte Differentiation Antigens; used with permission

Modified 10/14/99   mpr@mail.nih.gov