Abstract
The B-cell receptor CD22 binds sialic acid linked alpha-2-6 to terminal galactose residues on N-linked oligosaccharides associated with several cell-surface glycoproteins. The first of these sialoglycoproteins to be identified was the receptor-linked phosphotyrosine phosphatase CD45, which is required for antigen/CD3-induced T-cell activation. In the present work, we examine the effect of interaction between the extracellular domain of CD45 and CD22 on T-cell activation. Using soluble CD22-immunoglobulin fusion proteins and T cells expressing wild-type and chimeric CD45 forms, we show that engagement of CD45 by soluble CD22 can modulate early T-cell signals in antigen receptor/CD3-mediated stimulation. We also show that addition of sialic acid by beta-galactoside alpha-2,6-sialyltransferase to the CD22 molecule abrogates interactions between CD22 and its ligands. Together, these observations provide direct evidence for a functional role of the interaction between the extracellular domain of CD45 and a natural ligand and suggest another regulatory mechanism for CD22-mediated ligand engagement.
Full text
PDF![4026](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/603a/42095/951658d748c9/pnas01493-0402.png)
![4027](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/603a/42095/e1954154ee45/pnas01493-0403.png)
![4028](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/603a/42095/a4f1f4609ce6/pnas01493-0404.png)
![4029](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/603a/42095/d86290f4c4ab/pnas01493-0405.png)
![4030](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/603a/42095/49ad51519c72/pnas01493-0406.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Aruffo A., Kanner S. B., Sgroi D., Ledbetter J. A., Stamenkovic I. CD22-mediated stimulation of T cells regulates T-cell receptor/CD3-induced signaling. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10242–10246. doi: 10.1073/pnas.89.21.10242. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berridge M. J. Inositol trisphosphate and calcium signalling. Nature. 1993 Jan 28;361(6410):315–325. doi: 10.1038/361315a0. [DOI] [PubMed] [Google Scholar]
- Braesch-Andersen S., Stamenkovic I. Sialylation of the B lymphocyte molecule CD22 by alpha 2,6-sialyltransferase is implicated in the regulation of CD22-mediated adhesion. J Biol Chem. 1994 Apr 22;269(16):11783–11786. [PubMed] [Google Scholar]
- Clark E. A., Ledbetter J. A. Leukocyte cell surface enzymology: CD45 (LCA, T200) is a protein tyrosine phosphatase. Immunol Today. 1989 Jul;10(7):225–228. doi: 10.1016/0167-5699(89)90257-0. [DOI] [PubMed] [Google Scholar]
- Desai D. M., Sap J., Schlessinger J., Weiss A. Ligand-mediated negative regulation of a chimeric transmembrane receptor tyrosine phosphatase. Cell. 1993 May 7;73(3):541–554. doi: 10.1016/0092-8674(93)90141-c. [DOI] [PubMed] [Google Scholar]
- Hovis R. R., Donovan J. A., Musci M. A., Motto D. G., Goldman F. D., Ross S. E., Koretzky G. A. Rescue of signaling by a chimeric protein containing the cytoplasmic domain of CD45. Science. 1993 Apr 23;260(5107):544–546. doi: 10.1126/science.8475387. [DOI] [PubMed] [Google Scholar]
- Kanner S. B., Damle N. K., Blake J., Aruffo A., Ledbetter J. A. CD2/LFA-3 ligation induces phospholipase-C gamma 1 tyrosine phosphorylation and regulates CD3 signaling. J Immunol. 1992 Apr 1;148(7):2023–2029. [PubMed] [Google Scholar]
- Koretzky G. A., Kohmetscher M. A., Kadleck T., Weiss A. Restoration of T cell receptor-mediated signal transduction by transfection of CD45 cDNA into a CD45-deficient variant of the Jurkat T cell line. J Immunol. 1992 Aug 15;149(4):1138–1142. [PubMed] [Google Scholar]
- Koretzky G. A., Kohmetscher M., Ross S. CD45-associated kinase activity requires lck but not T cell receptor expression in the Jurkat T cell line. J Biol Chem. 1993 Apr 25;268(12):8958–8964. [PubMed] [Google Scholar]
- Koretzky G. A., Picus J., Schultz T., Weiss A. Tyrosine phosphatase CD45 is required for T-cell antigen receptor and CD2-mediated activation of a protein tyrosine kinase and interleukin 2 production. Proc Natl Acad Sci U S A. 1991 Mar 15;88(6):2037–2041. doi: 10.1073/pnas.88.6.2037. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koretzky G. A., Picus J., Thomas M. L., Weiss A. Tyrosine phosphatase CD45 is essential for coupling T-cell antigen receptor to the phosphatidyl inositol pathway. Nature. 1990 Jul 5;346(6279):66–68. doi: 10.1038/346066a0. [DOI] [PubMed] [Google Scholar]
- Leprince C., Draves K. E., Geahlen R. L., Ledbetter J. A., Clark E. A. CD22 associates with the human surface IgM-B-cell antigen receptor complex. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3236–3240. doi: 10.1073/pnas.90.8.3236. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Park D. J., Rho H. W., Rhee S. G. CD3 stimulation causes phosphorylation of phospholipase C-gamma 1 on serine and tyrosine residues in a human T-cell line. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5453–5456. doi: 10.1073/pnas.88.12.5453. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Powell L. D., Sgroi D., Sjoberg E. R., Stamenkovic I., Varki A. Natural ligands of the B cell adhesion molecule CD22 beta carry N-linked oligosaccharides with alpha-2,6-linked sialic acids that are required for recognition. J Biol Chem. 1993 Apr 5;268(10):7019–7027. [PubMed] [Google Scholar]
- Powell L. D., Varki A. The oligosaccharide binding specificities of CD22 beta, a sialic acid-specific lectin of B cells. J Biol Chem. 1994 Apr 8;269(14):10628–10636. [PubMed] [Google Scholar]
- Rabinovitch P. S., June C. H., Grossmann A., Ledbetter J. A. Heterogeneity among T cells in intracellular free calcium responses after mitogen stimulation with PHA or anti-CD3. Simultaneous use of indo-1 and immunofluorescence with flow cytometry. J Immunol. 1986 Aug 1;137(3):952–961. [PubMed] [Google Scholar]
- Sasaki K., Watanabe E., Kawashima K., Sekine S., Dohi T., Oshima M., Hanai N., Nishi T., Hasegawa M. Expression cloning of a novel Gal beta (1-3/1-4) GlcNAc alpha 2,3-sialyltransferase using lectin resistance selection. J Biol Chem. 1993 Oct 25;268(30):22782–22787. [PubMed] [Google Scholar]
- Sato T., Furukawa K., Autero M., Gahmberg C. G., Kobata A. Structural study of the sugar chains of human leukocyte common antigen CD45. Biochemistry. 1993 Nov 30;32(47):12694–12704. doi: 10.1021/bi00210a019. [DOI] [PubMed] [Google Scholar]
- Schwartz-Albiez R., Dörken B., Monner D. A., Moldenhauer G. CD22 antigen: biosynthesis, glycosylation and surface expression of a B lymphocyte protein involved in B cell activation and adhesion. Int Immunol. 1991 Jul;3(7):623–633. doi: 10.1093/intimm/3.7.623. [DOI] [PubMed] [Google Scholar]
- Secrist J. P., Karnitz L., Abraham R. T. T-cell antigen receptor ligation induces tyrosine phosphorylation of phospholipase C-gamma 1. J Biol Chem. 1991 Jul 5;266(19):12135–12139. [PubMed] [Google Scholar]
- Sgroi D., Stamenkovic I. The B-cell adhesion molecule CD22 is cross-species reactive and recognizes distinct sialoglycoproteins on different functional T-cell sub-populations. Scand J Immunol. 1994 May;39(5):433–438. doi: 10.1111/j.1365-3083.1994.tb03397.x. [DOI] [PubMed] [Google Scholar]
- Sgroi D., Varki A., Braesch-Andersen S., Stamenkovic I. CD22, a B cell-specific immunoglobulin superfamily member, is a sialic acid-binding lectin. J Biol Chem. 1993 Apr 5;268(10):7011–7018. [PubMed] [Google Scholar]
- Sjoberg E. R., Powell L. D., Klein A., Varki A. Natural ligands of the B cell adhesion molecule CD22 beta can be masked by 9-O-acetylation of sialic acids. J Cell Biol. 1994 Jul;126(2):549–562. doi: 10.1083/jcb.126.2.549. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stamenkovic I., Asheim H. C., Deggerdal A., Blomhoff H. K., Smeland E. B., Funderud S. The B cell antigen CD75 is a cell surface sialytransferase. J Exp Med. 1990 Aug 1;172(2):641–643. doi: 10.1084/jem.172.2.641. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stamenkovic I., Seed B. The B-cell antigen CD22 mediates monocyte and erythrocyte adhesion. Nature. 1990 May 3;345(6270):74–77. doi: 10.1038/345074a0. [DOI] [PubMed] [Google Scholar]
- Stamenkovic I., Sgroi D., Aruffo A., Sy M. S., Anderson T. The B lymphocyte adhesion molecule CD22 interacts with leukocyte common antigen CD45RO on T cells and alpha 2-6 sialyltransferase, CD75, on B cells. Cell. 1991 Sep 20;66(6):1133–1144. doi: 10.1016/0092-8674(91)90036-x. [DOI] [PubMed] [Google Scholar]
- Thomas M. L. The leukocyte common antigen family. Annu Rev Immunol. 1989;7:339–369. doi: 10.1146/annurev.iy.07.040189.002011. [DOI] [PubMed] [Google Scholar]
- Wang X., Vertino A., Eddy R. L., Byers M. G., Jani-Sait S. N., Shows T. B., Lau J. T. Chromosome mapping and organization of the human beta-galactoside alpha 2,6-sialyltransferase gene. Differential and cell-type specific usage of upstream exon sequences in B-lymphoblastoid cells. J Biol Chem. 1993 Feb 25;268(6):4355–4361. [PubMed] [Google Scholar]
- Weinstein J., Lee E. U., McEntee K., Lai P. H., Paulson J. C. Primary structure of beta-galactoside alpha 2,6-sialyltransferase. Conversion of membrane-bound enzyme to soluble forms by cleavage of the NH2-terminal signal anchor. J Biol Chem. 1987 Dec 25;262(36):17735–17743. [PubMed] [Google Scholar]
- Wilson G. L., Fox C. H., Fauci A. S., Kehrl J. H. cDNA cloning of the B cell membrane protein CD22: a mediator of B-B cell interactions. J Exp Med. 1991 Jan 1;173(1):137–146. doi: 10.1084/jem.173.1.137. [DOI] [PMC free article] [PubMed] [Google Scholar]