• B220
• CD45R
• CD45RA
• CD45RB
• CD45RC
• CD45RO
• EC 3.1.3.4
• Leukocyte Common Antigen, LCA
• T200
• Ly5

MAJOR LINKS FOR CD45  

• NCBI LocusLink Record: 5788
• Mendelian Inheritance in Man (OMIM): 151460
• SwissProt annotated protein record: P08575

• CD45 is a tyrosine phosphatase (EC 3.1.34), probably the dominant leukocyte plasma membrane located phosphatase (Tonks NK et al. 1988)

CELLULAR FUNCTION OF CD45  

• Critical requirement for T and B cell antigen receptor-mediated activation
• Possible requirement for receptor-mediated activation in other leukocytes (Pingel JT and Thomas ML 1989)

DISEASE RELEVANCE OF CD45 AND FUNCTION OF CD45 IN INTACT ANIMAL  

• Knock-out mice have defective thymocyte development, reduced numbers of mature T cells, and absent responses to T and B cell antigen receptor-mediated activation, (Kishihara T et al. 1993)
• Isoforms are the best available individual discriminators of naive and memory T cells, so clinical monitoring is being explored
• Target of immunosuppressive antibody treatment

• Families in which CD45 is a member
  • CD45-->protein tyrosine phosphatase receptor-->phosphatases

MOLECULAR STRUCTURE OF CD45  

• Long single chain type I transmembrane molecule (1120-1281 amino acids)
• About 391-552 amino acid extracellular domain. Differential splicing of 3 exons near the amino-terminus causes size variability in CD45
• Sequence of membrane proximal region of extracellular domain suggests 3 fibronectin type III domains (Okumura M et al. 1996)
• Long intracytoplasmic tail (about 707 amino acids) contains direct repeat of two phosphatase domains
• Only the 1st domain has significant phosphatase activity. Despite one conflicting report, the general opinion is that the second domain cannot have significant activity since critical amino acids necessary for catalytic activity are changed in the second domain**

MOLECULAR MASS OF CD45  

POST-TRANSCRIPTIONAL MODIFICATION OF CD45  

• The different isoforms of CD45 arise from variable splicing of exons 4, 5, and 6, which encode A, B, and C, determinants respectively, recognized by CD45RA, CD45RB and CD45RC antibodies respectively
• The 220k isoform contains A, B, and C determinants
• The 210k isoforms contain either A and B or B and C determinants
• The 200k isoform contains the B determinant; the 180k isoform lacks A, B and C determinants and is recognized by CD45RO antibodies

POST-TRANSLATIONAL MODIFICATION OF CD45  

• Extensive serine/threonine glycosylation near the N-terminus, particularly of differentially spliced exons
• Extensive N-glycosylation of the extracellular domain, especially in the membrane proximal FN type III domain*
• Phosphorylation of the cytoplasmic domain on serine and tyrosine has been observed*

SUBSTRATES FOR CD45  

ENZYMES WHICH MODIFY CD45   - No information

LIGANDS FOR CD45 AND MOLECULES ASSOCIATED WITH CD45  

• CD22 has been reported to bind to CD45RO. However, CD22 interaction with CD45 is not restricted to CD45RO but can occur with all CD45 isoforms, if properly sialyated (alpha 2,6-linked sialic acid), since CD22 is a lectin with specificity for such carbohydrate moieties

• Expressed, typically at high levels, on all hematopoietic cells
• A major component of the glycocalyx**
• Expression is at a higher density on lymphocytes, approximately 10% of surface area is CD45**
• While still abundant, the expression is lower on other leukocytes**
• Expression of different isoforms is characteristic of differentiated subsets of hematopoietic cells (for example CD45RA on naive/resting T cells and CD45RO on memory/activated T cells; CD45RO on cortical thymocytes and CD45RA on medullary thymocytes)
• Isoform patterns can change in response to cytokines. Thus, the expression patterns for a given population are generalities and not absolutes**
• Note simultaneous expression of multiple isoforms on a single cell type

• Major unresolved issue still is the physiological function of the extracellular domain and the significance of the different isoforms
• CD45-deficient macrophages are dysregulated in integrin-mediated adhesion due to the inability to regulate the lyn and hck kinases (Roach et al. 1997}**

SELECTION OF OTHER CD45-SPECIFIC REFERENCE MAB  

REVIEWS

1. Barclay AN and McCall MN. CD45; from alloantigen to mapping of restricted epitopes using recombinant soluble CD45 isoforms. Biochem. Soc. Trans. 1992 20:161 PubMed

2. Trowbridge IS and Thomas ML. CD45: an emerging role as a protein tyrosine phosphatase required for lymphocyte activation and development. Annu. Rev. Immunol. 1993 12:85 PubMed

PRIMARY CITATIONS

3. Beverley PCL. 1980. in Production and Use of Monoclonal Antibodies in Transplantation Immunology. In Transplantation and Clinical Immunology XI. pp 87-94, eds Touraine JL et al, Excerpta Medica Amsterdam.

4. Kishihara K, Penninger J, Wallace VA, Kundig TM, Kawai K, Wakeham A, Timms E, Pfeffer K, Ohashi PS, Thomas ML and et al. Normal B lymphocyte development but impaired T cell maturation in CD45-exon6 protein tyrosine phosphatase-deficient mice. Cell 1993 74:143 PubMed

5. Morimoto C, Letvin NL, Distaso JA, Aldrich WR and Schlossman SF. The isolation and characterization of the human suppressor inducer T cell subset. J. Immunol. 1985 134:1508 PubMed

6. Okumura M, Matthews RJ, Robb B, Litman GW, Bork P and Thomas ML. Comparison of CD45 extracellular domain sequences from divergent vertebrate species suggests the conservation of three fibronectin type III domains. J. Immunol. 1996 157:1569 PubMed

7. Perillo NL, Pace KE, Seilhamer JJ and Baum LG. Apoptosis of T cells mediated by galectin-1. Nature 1995 378:736 PubMed

8. Pingel JT and Thomas ML. Evidence that the leukocyte-common antigen is required for antigen-induced T lymphocyte proliferation. Cell 1989 58:1055 PubMed

9. Pulido R, Cebrian M, Acevedo A, de Landazuri MO and Sanchez-Madrid F. Comparative biochemical and tissue distribution study of four distinct CD45 antigen specificities. J. Immunol. 1988 140:3851 PubMed

10. Roach T, Slater S, Koval M, White L, McFarland EC, Okumura M, Thomas M and Brown E. CD45 regulates Src family member kinase activity associated with macrophage integrin-mediated adhesion. Curr. Biol. 1997 7:408 PubMed

11. Terry LA, Brown MH and Beverley PC. The monoclonal antibody, UCHL1, recognizes a 180,000 MW component of the human leucocyte-common antigen, CD45. Immunology 1988 64:331 PubMed

12. Tonks NK, Charbonneau H, Diltz CD, Fischer EH and Walsh KA. Demonstration that the leukocyte common antigen CD45 is a protein tyrosine phosphatase. Biochemistry 1988 27:8695 PubMed

13. Zapata JM, Pulido R, Acevedo A, Sanchez-Madrid F and de Landazuri MO. Human CD45RC specificity. A novel marker for T cells at different maturation and activation stages. J. Immunol. 1994 152:3852 PubMed

WWW RESOURCES

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

Modified 10/15/99   mpr@mail.nih.gov