Abstract
CD6 is a 130-kD glycoprotein expressed on the surface of thymocytes and peripheral blood T cells that is involved in TCR-mediated T cell activation. In thymus, CD6 mediates interactions between thymocytes and thymic epithelial (TE) cells. In indirect immunofluorescence assays, a recombinant CD6-immunoglobulin fusion protein (CD6-Rg) bound to cultured human TE cells and to thymic fibroblasts. CD6-Rg binding to TF and TE cells was trypsin sensitive, and 54 +/- 4% of binding was divalent cation dependent. By screening the blind panel of 479 monoclonal antibodies (mAbs) from the 5th International Workshop on Human Leukocyte Differentiation Antigens for expression on human TE cells and for the ability to block CD6-Rg binding to TE cells, we found one mAb (J4-81) that significantly inhibited the binding of CD6-Rg to TE cells (60 +/- 7% inhibition). A second mAb to the surface antigen identified by mAb J4-81, J3-119, enhanced the binding of CD6-Rg to TE cells by 48 +/- 5%. Using covalent cross-linking and trypsin digestion, we found that mAb J4-81 and CD6-Rg both bound to the same 100-kD glycoprotein (CD6L-100) on the surface of TE cells. These data demonstrate that a 100-kD glycoprotein on TE cells detected by mAb J4- 81 is a ligand for CD6.
Full Text
The Full Text of this article is available as a PDF (929.1 KB).
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]
- Aruffo A., Melnick M. B., Linsley P. S., Seed B. The lymphocyte glycoprotein CD6 contains a repeated domain structure characteristic of a new family of cell surface and secreted proteins. J Exp Med. 1991 Oct 1;174(4):949–952. doi: 10.1084/jem.174.4.949. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Denning S. M., Tuck D. T., Vollger L. W., Springer T. A., Singer K. H., Haynes B. F. Monoclonal antibodies to CD2 and lymphocyte function-associated antigen 3 inhibit human thymic epithelial cell-dependent mature thymocyte activation. J Immunol. 1987 Oct 15;139(8):2573–2578. [PubMed] [Google Scholar]
- Gangemi R. M., Swack J. A., Gaviria D. M., Romain P. L. Anti-T12, an anti-CD6 monoclonal antibody, can activate human T lymphocytes. J Immunol. 1989 Oct 15;143(8):2439–2447. [PubMed] [Google Scholar]
- Giunta M., Favre A., Ramarli D., Grossi C. E., Corte G. A novel integrin involved in thymocyte-thymic epithelial cell interactions. J Exp Med. 1991 Jun 1;173(6):1537–1548. doi: 10.1084/jem.173.6.1537. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haynes B. F., Hensley L. L., Jegasothy B. V. Differentiation of human T lymphocytes: II. Phenotypic difference in skin and blood malignant T-cells in cutaneous T-cell lymphoma. J Invest Dermatol. 1982 Apr;78(4):323–326. doi: 10.1111/1523-1747.ep12507406. [DOI] [PubMed] [Google Scholar]
- Imhof B. A., Ruiz P., Hesse B., Palacios R., Dunon D. EA-1, a novel adhesion molecule involved in the homing of progenitor T lymphocytes to the thymus. J Cell Biol. 1991 Sep;114(5):1069–1078. doi: 10.1083/jcb.114.5.1069. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kamoun M., Kadin M. E., Martin P. J., Nettleton J., Hansen J. A. A novel human T cell antigen preferentially expressed on mature T cells and shared by both well and poorly differentiated B cell leukemias and lymphomas. J Immunol. 1981 Sep;127(3):987–991. [PubMed] [Google Scholar]
- Ledbetter J. A., Norris N. A., Grossmann A., Grosmaire L. S., June C. H., Uckun F. M., Cosand W. L., Rabinovitch P. S. Enhanced transmembrane signalling activity of monoclonal antibody heteroconjugates suggests molecular interactions between receptors on the T cell surface. Mol Immunol. 1989 Feb;26(2):137–145. doi: 10.1016/0161-5890(89)90095-3. [DOI] [PubMed] [Google Scholar]
- Mayer B., Funke I., Seed B., Riethmüller G., Weiss E. Expression of the CD6 T lymphocyte differentiation antigen in normal human brain. J Neuroimmunol. 1990 Sep-Oct;29(1-3):193–202. doi: 10.1016/0165-5728(90)90162-g. [DOI] [PubMed] [Google Scholar]
- Morimoto C., Rudd C. E., Letvin N. L., Hagan M., Schlossman S. F. 2H1--a novel antigen involved in T lymphocyte triggering. J Immunol. 1988 Apr 1;140(7):2165–2170. [PubMed] [Google Scholar]
- Osorio L. M., Garcia C. A., Jondal M., Chow S. C. The anti-CD6 mAb, IOR-T1, defined a new epitope on the human CD6 molecule that induces greater responsiveness in T cell receptor/CD3-mediated T cell proliferation. Cell Immunol. 1994 Mar;154(1):123–133. doi: 10.1006/cimm.1994.1062. [DOI] [PubMed] [Google Scholar]
- Patel D. D., Haynes B. F. Cell adhesion molecules involved in intrathymic T cell development. Semin Immunol. 1993 Aug;5(4):282–292. doi: 10.1006/smim.1993.1032. [DOI] [PubMed] [Google Scholar]
- Patel D. D., Pickup D. J., Joklik W. K. Isolation of cowpox virus A-type inclusions and characterization of their major protein component. Virology. 1986 Mar;149(2):174–189. doi: 10.1016/0042-6822(86)90119-4. [DOI] [PubMed] [Google Scholar]
- Pawlowski T. J., Staerz U. D. Thymic education--T cells do it for themselves. Immunol Today. 1994 May;15(5):205–209. doi: 10.1016/0167-5699(94)90244-5. [DOI] [PubMed] [Google Scholar]
- Pesando J. M., Hoffman P., Abed M. Antibody-induced antigenic modulation is antigen dependent: characterization of 22 proteins on a malignant human B cell line. J Immunol. 1986 Dec 1;137(11):3689–3695. [PubMed] [Google Scholar]
- Rasmussen R. A., Counts S. L., Daley J. F., Schlossman S. F. Isolation and characterization of CD6- T cells from peripheral blood. J Immunol. 1994 Jan 15;152(2):527–536. [PubMed] [Google Scholar]
- Reinherz E. L., Meuer S., Fitzgerald K. A., Hussey R. E., Levine H., Schlossman S. F. Antigen recognition by human T lymphocytes is linked to surface expression of the T3 molecular complex. Cell. 1982 Oct;30(3):735–743. doi: 10.1016/0092-8674(82)90278-1. [DOI] [PubMed] [Google Scholar]
- Singer K. H., Denning S. M., Whichard L. P., Haynes B. F. Thymocyte LFA-1 and thymic epithelial cell ICAM-1 molecules mediate binding of activated human thymocytes to thymic epithelial cells. J Immunol. 1990 Apr 15;144(8):2931–2939. [PubMed] [Google Scholar]
- Singer K. H., Harden E. A., Robertson A. L., Lobach D. F., Haynes B. F. In vitro growth and phenotypic characterization of mesodermal-derived and epithelial components of normal and abnormal human thymus. Hum Immunol. 1985 Jul;13(3):161–176. doi: 10.1016/0198-8859(85)90009-6. [DOI] [PubMed] [Google Scholar]
- Singer K. H., Scearce R. M., Tuck D. T., Whichard L. P., Denning S. M., Haynes B. F. Removal of fibroblasts from human epithelial cell cultures with use of a complement fixing monoclonal antibody reactive with human fibroblasts and monocytes/macrophages. J Invest Dermatol. 1989 Feb;92(2):166–170. doi: 10.1111/1523-1747.ep12276685. [DOI] [PubMed] [Google Scholar]
- Soiffer R. J., Murray C., Mauch P., Anderson K. C., Freedman A. S., Rabinowe S. N., Takvorian T., Robertson M. J., Spector N., Gonin R. Prevention of graft-versus-host disease by selective depletion of CD6-positive T lymphocytes from donor bone marrow. J Clin Oncol. 1992 Jul;10(7):1191–1200. doi: 10.1200/JCO.1992.10.7.1191. [DOI] [PubMed] [Google Scholar]
- Swack J. A., Gangemi R. M., Rudd C. E., Morimoto C., Schlossman S. F., Romain P. L. Structural characterization of CD6: properties of two distinct epitopes involved in T cell activation. Mol Immunol. 1989 Nov;26(11):1037–1049. doi: 10.1016/0161-5890(89)90068-0. [DOI] [PubMed] [Google Scholar]
- Telen M. J., Eisenbarth G. S., Haynes B. F. Human erythrocyte antigens. Regulation of expression of a novel erythrocyte surface antigen by the inhibitor Lutheran In(Lu) gene. J Clin Invest. 1983 Jun;71(6):1878–1886. doi: 10.1172/JCI110943. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Utsumi K., Sawada M., Narumiya S., Nagamine J., Sakata T., Iwagami S., Kita Y., Teraoka H., Hirano H., Ogata M. Adhesion of immature thymocytes to thymic stromal cells through fibronectin molecules and its significance for the induction of thymocyte differentiation. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5685–5689. doi: 10.1073/pnas.88.13.5685. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vollger L. W., Tuck D. T., Springer T. A., Haynes B. F., Singer K. H. Thymocyte binding to human thymic epithelial cells is inhibited by monoclonal antibodies to CD-2 and LFA-3 antigens. J Immunol. 1987 Jan 15;138(2):358–363. [PubMed] [Google Scholar]
- Wee S., Schieven G. L., Kirihara J. M., Tsu T. T., Ledbetter J. A., Aruffo A. Tyrosine phosphorylation of CD6 by stimulation of CD3: augmentation by the CD4 and CD2 coreceptors. J Exp Med. 1993 Jan 1;177(1):219–223. doi: 10.1084/jem.177.1.219. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wee S., Wang W. C., Farr A. G., Nelson A. J., Patel D. D., Haynes B. F., Linsley P. S., Aruffo A. Characterization of a CD6 ligand(s) expressed on human- and murine-derived cell lines and murine lymphoid tissues. Cell Immunol. 1994 Oct 15;158(2):353–364. doi: 10.1006/cimm.1994.1282. [DOI] [PubMed] [Google Scholar]
