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J Exp Med. 1995 June 1; 181(6): 2213–2220.
PMCID: PMC2192054

Cloning, mapping, and characterization of activated leukocyte-cell adhesion molecule (ALCAM), a CD6 ligand

Abstract

Antibody-blocking studies have demonstrated the role of CD6 in thymocyte-thymic epithelial (TE) cell adhesion. Here we report that CD6 expressed by COS cells mediates adhesion to TE cells and that this interaction is specifically blocked with an anti-CD6 monoclonal antibody (mAb) or with a mAb (J4-81) that recognized a TE cell antigen. We isolated and expressed a cDNA clone encoding this antigen and show that COS cells transfected with this cDNA bind a CD6 immunoglobulin fusion protein (CD6-Rg). This antigen, which we named ALCAM (activated leukocyte-cell adhesion molecule) because of its expression on activated leukocytes, appears to be the human homologue of the chicken neural adhesion molecule BEN/SC-1/DM-GRASP. The gene was mapped to human chromosome 3q13.1-q13.2 by fluorescence in situ hybridization of cDNA probes to metaphase chromosomes. We prepared an ALCAM-Rg fusion protein and showed that it binds to COS cell transfectants expressing CD6, demonstrating that ALCAM is a CD6 ligand. The observations that ALCAM is also expressed by activated leukocytes and that both ALCAM and CD6 are expressed in the brain suggest that ALCAM-CD6 interactions may play a role in the binding of T and B cells to activated leukocytes, as well as in interactions between cells of the nervous system.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Peduzzi JD, Irwin MH, Geisert EE., Jr Distribution and characteristics of a 90 kDa protein, KG-CAM, in the rat CNS. Brain Res. 1994 Mar 21;640(1-2):296–307. [PubMed]
  • Aruffo A, Melnick MB, Linsley PS, 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. [PMC free article] [PubMed]
  • Reinherz EL, Meuer S, Fitzgerald KA, Hussey RE, Levine H, Schlossman SF. Antigen recognition by human T lymphocytes is linked to surface expression of the T3 molecular complex. Cell. 1982 Oct;30(3):735–743. [PubMed]
  • Morimoto C, Rudd CE, Letvin NL, Hagan M, Schlossman SF. 2H1--a novel antigen involved in T lymphocyte triggering. J Immunol. 1988 Apr 1;140(7):2165–2170. [PubMed]
  • 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. [PubMed]
  • Resnick D, Pearson A, Krieger M. The SRCR superfamily: a family reminiscent of the Ig superfamily. Trends Biochem Sci. 1994 Jan;19(1):5–8. [PubMed]
  • Kodama T, Freeman M, Rohrer L, Zabrecky J, Matsudaira P, Krieger M. Type I macrophage scavenger receptor contains alpha-helical and collagen-like coiled coils. Nature. 1990 Feb 8;343(6258):531–535. [PubMed]
  • Jones NH, Clabby ML, Dialynas DP, Huang HJ, Herzenberg LA, Strominger JL. Isolation of complementary DNA clones encoding the human lymphocyte glycoprotein T1/Leu-1. Nature. 323(6086):346–349. [PubMed]
  • Huang HJ, Jones NH, Strominger JL, Herzenberg LA. Molecular cloning of Ly-1, a membrane glycoprotein of mouse T lymphocytes and a subset of B cells: molecular homology to its human counterpart Leu-1/T1 (CD5). Proc Natl Acad Sci U S A. 1987 Jan;84(1):204–208. [PubMed]
  • Law SK, Micklem KJ, Shaw JM, Zhang XP, Dong Y, Willis AC, Mason DY. A new macrophage differentiation antigen which is a member of the scavenger receptor superfamily. Eur J Immunol. 1993 Sep;23(9):2320–2325. [PubMed]
  • Wijngaard PL, Metzelaar MJ, MacHugh ND, Morrison WI, Clevers HC. Molecular characterization of the WC1 antigen expressed specifically on bovine CD4-CD8- gamma delta T lymphocytes. J Immunol. 1992 Nov 15;149(10):3273–3277. [PubMed]
  • Gangemi RM, Swack JA, Gaviria DM, Romain PL. Anti-T12, an anti-CD6 monoclonal antibody, can activate human T lymphocytes. J Immunol. 1989 Oct 15;143(8):2439–2447. [PubMed]
  • Swack JA, Gangemi RM, Rudd CE, Morimoto C, Schlossman SF, Romain PL. Structural characterization of CD6: properties of two distinct epitopes involved in T cell activation. Mol Immunol. 1989 Nov;26(11):1037–1049. [PubMed]
  • Ledbetter JA, Norris NA, Grossmann A, Grosmaire LS, June CH, Uckun FM, Cosand WL, Rabinovitch PS. 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. [PubMed]
  • Bott CM, Doshi JB, Morimoto C, Romain PL, Fox DA. Activation of human T cells through CD6: functional effects of a novel anti-CD6 monoclonal antibody and definition of four epitopes of the CD6 glycoprotein. Int Immunol. 1993 Jul;5(7):783–792. [PubMed]
  • Bott CM, Doshi JB, Li LL, McMurtry SA, Sanders JL, Fox DA. Transcriptional regulation of CD6 expression on human T lymphocytes by phorbol ester. J Immunol. 1994 Jul 1;153(1):1–9. [PubMed]
  • Swack JA, Mier JW, Romain PL, Hull SR, Rudd CE. Biosynthesis and post-translational modification of CD6, a T cell signal-transducing molecule. J Biol Chem. 1991 Apr 15;266(11):7137–7143. [PubMed]
  • Wee S, Schieven GL, Kirihara JM, Tsu TT, Ledbetter JA, 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. [PMC free article] [PubMed]
  • Cardenas L, Carrera AC, Yague E, Pulido R, Sánchez-Madrid F, de Landázuri MO. Phosphorylation-dephosphorylation of the CD6 glycoprotein renders two isoforms of 130 and 105 kilodaltons. Effect of serum and protein kinase C activators. J Immunol. 1990 Sep 1;145(5):1450–1455. [PubMed]
  • Kirkman RL, Araujo JL, Busch GJ, Carpenter CB, Milford EL, Reinherz EL, Schlossman SF, Strom TB, Tilney NL. Treatment of acute renal allograft rejection with monoclonal anti-T12 antibody. Transplantation. 1983 Dec;36(6):620–626. [PubMed]
  • Reinherz EL, Geha R, Rappeport JM, Wilson M, Penta AC, Hussey RE, Fitzgerald KA, Daley JF, Levine H, Rosen FS, et al. Reconstitution after transplantation with T-lymphocyte-depleted HLA haplotype-mismatched bone marrow for severe combined immunodeficiency. Proc Natl Acad Sci U S A. 1982 Oct;79(19):6047–6051. [PubMed]
  • Wee S, Wang WC, Farr AG, Nelson AJ, Patel DD, Haynes BF, Linsley PS, 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. [PubMed]
  • Patel DD, Wee SF, Whichard LP, Bowen MA, Pesando JM, Aruffo A, Haynes BF. Identification and characterization of a 100-kD ligand for CD6 on human thymic epithelial cells. J Exp Med. 1995 Apr 1;181(4):1563–1568. [PMC free article] [PubMed]
  • Vollger LW, Tuck DT, Springer TA, Haynes BF, Singer KH. 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]
  • Pesando JM, 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]
  • Singer KH, Harden EA, Robertson AL, Lobach DF, Haynes BF. 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. [PubMed]
  • Singer KH, Scearce RM, Tuck DT, Whichard LP, Denning SM, Haynes BF. 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. [PubMed]
  • Liao HX, Levesque MC, Patton K, Bergamo B, Jones D, Moody MA, Telen MJ, Haynes BF. Regulation of human CD44H and CD44E isoform binding to hyaluronan by phorbol myristate acetate and anti-CD44 monoclonal and polyclonal antibodies. J Immunol. 1993 Dec 1;151(11):6490–6499. [PubMed]
  • Bowen MA, Olsen KJ, Cheng L, Avila D, Podack ER. Functional effects of CD30 on a large granular lymphoma cell line, YT. Inhibition of cytotoxicity, regulation of CD28 and IL-2R, and induction of homotypic aggregation. J Immunol. 1993 Dec 1;151(11):5896–5906. [PubMed]
  • Maresh GA, Wang WC, Beam KS, Malacko AR, Hellström I, Hellström KE, Marquardt H. Differential processing and secretion of the melanoma-associated ME20 antigen. Arch Biochem Biophys. 1994 May 15;311(1):95–102. [PubMed]
  • Aruffo A, Seed B. Molecular cloning of a CD28 cDNA by a high-efficiency COS cell expression system. Proc Natl Acad Sci U S A. 1987 Dec;84(23):8573–8577. [PubMed]
  • Pourquié O, Corbel C, Le Caer JP, Rossier J, Le Douarin NM. BEN, a surface glycoprotein of the immunoglobulin superfamily, is expressed in a variety of developing systems. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5261–5265. [PubMed]
  • Tanaka H, Matsui T, Agata A, Tomura M, Kubota I, McFarland KC, Kohr B, Lee A, Phillips HS, Shelton DL. Molecular cloning and expression of a novel adhesion molecule, SC1. Neuron. 1991 Oct;7(4):535–545. [PubMed]
  • Burns FR, von Kannen S, Guy L, Raper JA, Kamholz J, Chang S. DM-GRASP, a novel immunoglobulin superfamily axonal surface protein that supports neurite extension. Neuron. 1991 Aug;7(2):209–220. [PubMed]
  • Corbel C, Bluestein HG, Pourquie O, Vaigot P, Le Douarin NM. An antigen expressed by avian neuronal cells is also expressed by activated T lymphocytes. Cell Immunol. 1992 Apr 15;141(1):99–110. [PubMed]
  • Laessing U, Giordano S, Stecher B, Lottspeich F, Stuermer CA. Molecular characterization of fish neurolin: a growth-associated cell surface protein and member of the immunoglobulin superfamily in the fish retinotectal system with similarities to chick protein DM-GRASP/SC-1/BEN. Differentiation. 1994 Apr;56(1-2):21–29. [PubMed]
  • Neeper M, Schmidt AM, Brett J, Yan SD, Wang F, Pan YC, Elliston K, Stern D, Shaw A. Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins. J Biol Chem. 1992 Jul 25;267(21):14998–15004. [PubMed]
  • Lehmann JM, Riethmüller G, Johnson JP. MUC18, a marker of tumor progression in human melanoma, shows sequence similarity to the neural cell adhesion molecules of the immunoglobulin superfamily. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9891–9895. [PubMed]
  • Tsuge I, Utsumi KR, Ueda R, Takamoto S, Takahashi T. Assignment of gene coding human T-cell differentiation antigen, Tp120, to chromosome 11. Somat Cell Mol Genet. 1985 May;11(3):217–222. [PubMed]
  • Bello MJ, Salagnon N, Rey JA, Guichaoua MR, Bergé-Lefranc JL, Jordan BR, Luciani JM. Precise in situ localization of NCAM, ETS1, and D11S29 on human meiotic chromosomes. Cytogenet Cell Genet. 1989;52(1-2):7–10. [PubMed]
  • Sers C, Kirsch K, Rothbächer U, Riethmüller G, Johnson JP. Genomic organization of the melanoma-associated glycoprotein MUC18: implications for the evolution of the immunoglobulin domains. Proc Natl Acad Sci U S A. 1993 Sep 15;90(18):8514–8518. [PubMed]
  • Campbell IG, Foulkes WD, Senger G, Trowsdale J, Garin-Chesa P, Rettig WJ. Molecular cloning of the B-CAM cell surface glycoprotein of epithelial cancers: a novel member of the immunoglobulin superfamily. Cancer Res. 1994 Nov 15;54(22):5761–5765. [PubMed]
  • McCaughan GW, Clark MJ, Hurst J, Grosveld F, Barclay AN. The gene for MRC OX-2 membrane glycoprotein is localized on human chromosome 3. Immunogenetics. 1987;25(2):133–135. [PubMed]
  • Douglas J, Albertson DG, Barclay AN, Davis M, Rabbitts PH. RFLP and mapping of human MOX-1 gene on chromosome 3. Nucleic Acids Res. 1988 Sep 26;16(18):9067–9067. [PMC free article] [PubMed]
  • Singer KH, Denning SM, Whichard LP, Haynes BF. 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]
  • Giunta M, Favre A, Ramarli D, Grossi CE, Corte G. A novel integrin involved in thymocyte-thymic epithelial cell interactions. J Exp Med. 1991 Jun 1;173(6):1537–1548. [PMC free article] [PubMed]
  • Imhof BA, 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. [PMC free article] [PubMed]
  • Utsumi K, Sawada M, Narumiya S, Nagamine J, Sakata T, Iwagami S, Kita Y, Teraoka H, Hirano H, Ogata M, et al. 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. [PubMed]
  • Pourquié O, Coltey M, Thomas JL, Le Douarin NM. A widely distributed antigen developmentally regulated in the nervous system. Development. 1990 Aug;109(4):743–752. [PubMed]
  • Appel SH, Engelhardt JI, García J, Stefani E. Autoimmunity and ALS: a comparison of animal models of immune-mediated motor neuron destruction and human ALS. Adv Neurol. 1991;56:405–412. [PubMed]
  • McGeer PL, McGeer EG, Kawamata T, Yamada T, Akiyama H. Reactions of the immune system in chronic degenerative neurological diseases. Can J Neurol Sci. 1991 Aug;18(3 Suppl):376–379. [PubMed]
  • Rowland LP. Ten central themes in a decade of ALS research. Adv Neurol. 1991;56:3–23. [PubMed]
  • Van de Velde H, von Hoegen I, Luo W, Parnes JR, Thielemans K. The B-cell surface protein CD72/Lyb-2 is the ligand for CD5. Nature. 1991 Jun 20;351(6328):662–665. [PubMed]

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