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J Exp Med. 1996 Sep 1; 184(3): 811–819.
PMCID: PMC2192762

Identification of a novel inducible cell-surface ligand of CD5 on activated lymphocytes


CD5 is a 67-kD glycoprotein that is expressed on most T lymphocytes and on a subset of mature B cells. Although its physiologic function is unknown, several lines of evidence suggest that CD5 may play a role in the regulation of T cell activation and in T cell-antigen presenting cell interactions. Using a CD5-immunoglobulin fusion protein (CD5Rg, for receptorglobulin) we have uncovered a new CD5 ligand (CD5L) expressed on the surface of activated splenocytes. Stimulation of murine splenocytes with anti-CD3 and anti-CD28 antibodies induce transient expression of CD5L on B lymphocytes that lasts for approximately 72 h. Binding of CD5Rg to activated splenocytes is trypsin resistant and independent of divalent cations. However, it is pronase sensitive and dependent on N-linked glycosylation of CD5, since treatment of CD5Rg with PNGaseF on N-glycanase completely abrogates its ability to bind activated splenocytes. It addition to splenocytes, CD5L is expressed on activated murine T cell clones. Immunoprecipitation, antibody, and recombinant protein blocking studies indicate that CD5L is distinct from CD72, which has been proposed to be a CD5 ligand. To determine whether CD5-CD5L interaction might play a role in vivo, we tested the effect of CD5Rg in a murine model of antibody-mediated membranous glomerulonephritis. Injection of CD5Rg was found to abrogate development of the disease. Taken together, our results help identify a novel ligand of CD5 and propose a role for CD5 in the regulation of immune responses.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • 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]
  • Casali P, Notkins AL. CD5+ B lymphocytes, polyreactive antibodies and the human B-cell repertoire. Immunol Today. 1989 Nov;10(11):364–368. [PubMed]
  • Ishida H, Hastings R, Kearney J, Howard M. Continuous anti-interleukin 10 antibody administration depletes mice of Ly-1 B cells but not conventional B cells. J Exp Med. 1992 May 1;175(5):1213–1220. [PMC free article] [PubMed]
  • June CH, Rabinovitch PS, Ledbetter JA. CD5 antibodies increase intracellular ionized calcium concentration in T cells. J Immunol. 1987 May 1;138(9):2782–2792. [PubMed]
  • Ledbetter JA, Martin PJ, Spooner CE, Wofsy D, Tsu TT, Beatty PG, Gladstone P. Antibodies to Tp67 and Tp44 augment and sustain proliferative responses of activated T cells. J Immunol. 1985 Oct;135(4):2331–2336. [PubMed]
  • Spertini F, Stohl W, Ramesh N, Moody C, Geha RS. Induction of human T cell proliferation by a monoclonal antibody to CD5. J Immunol. 1991 Jan 1;146(1):47–52. [PubMed]
  • Alberola-Ila J, Places L, Cantrell DA, Vives J, Lozano F. Intracellular events involved in CD5-induced human T cell activation and proliferation. J Immunol. 1992 Mar 1;148(5):1287–1293. [PubMed]
  • Stanton T, Stevens TL, Ledbetter JA, Wofsy D. Anti-Ly-1 antibody induces interleukin 2 release from T cells. J Immunol. 1986 Mar 1;136(5):1734–1737. [PubMed]
  • Davies AA, Ley SC, Crumpton MJ. CD5 is phosphorylated on tyrosine after stimulation of the T-cell antigen receptor complex. Proc Natl Acad Sci U S A. 1992 Jul 15;89(14):6368–6372. [PMC free article] [PubMed]
  • Raab M, Yamamoto M, Rudd CE. The T-cell antigen CD5 acts as a receptor and substrate for the protein-tyrosine kinase p56lck. Mol Cell Biol. 1994 May;14(5):2862–2870. [PMC free article] [PubMed]
  • Tarakhovsky A, Kanner SB, Hombach J, Ledbetter JA, Müller W, Killeen N, Rajewsky K. A role for CD5 in TCR-mediated signal transduction and thymocyte selection. Science. 1995 Jul 28;269(5223):535–537. [PubMed]
  • Sun D, Branum K, Sun Q. Prevention of experimental autoimmune encephalomyelitis in Lewis rats by treatment with an anti-rat CD5 antibody (OX19). Cell Immunol. 1992 Dec;145(2):263–271. [PubMed]
  • Plater-Zyberk C, Taylor PC, Blaylock MG, Maini RN. Anti-CD5 therapy decreases severity of established disease in collagen type II-induced arthritis in DBA/1 mice. Clin Exp Immunol. 1994 Dec;98(3):442–447. [PMC free article] [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]
  • Luo W, Van de Velde H, von Hoegen I, Parnes JR, Thielemans K. Ly-1 (CD5), a membrane glycoprotein of mouse T lymphocytes and a subset of B cells, is a natural ligand of the B cell surface protein Lyb-2 (CD72). J Immunol. 1992 Mar 15;148(6):1630–1634. [PubMed]
  • Snow EC, Mond JJ, Subbarao B. Enhancement by monoclonal anti-Lyb-2 antibody of antigen-specific B lymphocyte expansion stimulated by TNP-Ficoll and T lymphocyte-derived factors. J Immunol. 1986 Sep 15;137(6):1793–1796. [PubMed]
  • Kamal M, Katira A, Gordon J. Stimulation of B lymphocytes via CD72 (human Lyb-2). Eur J Immunol. 1991 Jun;21(6):1419–1424. [PubMed]
  • Subbarao B, Mosier DE. Induction of B lymphocyte proliferation by monoclonal anti-Lyb 2 antibody. J Immunol. 1983 May;130(5):2033–2037. [PubMed]
  • Assmann KJ, Tangelder MM, Lange WP, Tadema TM, Koene RA. Membranous glomerulonephritis in the mouse. Kidney Int. 1983 Sep;24(3):303–312. [PubMed]
  • Biancone L, Andres G, Ahn H, DeMartino C, Stamenkovic I. Inhibition of the CD40-CD40ligand pathway prevents murine membranous glomerulonephritis. Kidney Int. 1995 Aug;48(2):458–468. [PubMed]
  • Aruffo A, Stamenkovic I, Melnick M, Underhill CB, Seed B. CD44 is the principal cell surface receptor for hyaluronate. Cell. 1990 Jun 29;61(7):1303–1313. [PubMed]
  • Sy MS, Guo YJ, Stamenkovic I. Inhibition of tumor growth in vivo with a soluble CD44-immunoglobulin fusion protein. J Exp Med. 1992 Aug 1;176(2):623–627. [PMC free article] [PubMed]
  • Hollenbaugh D, Grosmaire LS, Kullas CD, Chalupny NJ, Braesch-Andersen S, Noelle RJ, Stamenkovic I, Ledbetter JA, Aruffo A. The human T cell antigen gp39, a member of the TNF gene family, is a ligand for the CD40 receptor: expression of a soluble form of gp39 with B cell co-stimulatory activity. EMBO J. 1992 Dec;11(12):4313–4321. [PMC free article] [PubMed]
  • Sgroi D, Cohen RN, Lingenheld EG, Strong MK, Binder T, Goldschneider I, Greiner D, Grunnet M, Clark RB. T cell lines derived from the spinal cords of mice with experimental allergic encephalomyelitis are self reactive. J Immunol. 1986 Sep 15;137(6):1850–1854. [PubMed]
  • Rogers PR, Pilapil S, Hayakawa K, Romain PL, Parker DC. CD45 alternative exon expression in murine and human CD4+ T cell subsets. J Immunol. 1992 Jun 15;148(12):4054–4065. [PubMed]
  • Kuiper HM, Brouwer M, Linsley PS, van Lier RA. Activated T cells can induce high levels of CTLA-4 expression on B cells. J Immunol. 1995 Aug 15;155(4):1776–1783. [PubMed]
  • Bevilacqua MP, Nelson RM. Selectins. J Clin Invest. 1993 Feb;91(2):379–387. [PMC free article] [PubMed]
  • 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]
  • Crocker PR, Mucklow S, Bouckson V, McWilliam A, Willis AC, Gordon S, Milon G, Kelm S, Bradfield P. Sialoadhesin, a macrophage sialic acid binding receptor for haemopoietic cells with 17 immunoglobulin-like domains. EMBO J. 1994 Oct 3;13(19):4490–4503. [PMC free article] [PubMed]
  • Freeman SD, Kelm S, Barber EK, Crocker PR. Characterization of CD33 as a new member of the sialoadhesin family of cellular interaction molecules. Blood. 1995 Apr 15;85(8):2005–2012. [PubMed]
  • Aruffo A, Kanner SB, Sgroi D, Ledbetter JA, 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. [PMC free article] [PubMed]
  • Sgroi D, Koretzky GA, Stamenkovic I. Regulation of CD45 engagement by the B-cell receptor CD22. Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):4026–4030. [PMC free article] [PubMed]
  • Wyss DF, Choi JS, Li J, Knoppers MH, Willis KJ, Arulanandam AR, Smolyar A, Reinherz EL, Wagner G. Conformation and function of the N-linked glycan in the adhesion domain of human CD2. Science. 1995 Sep 1;269(5228):1273–1278. [PubMed]
  • Sgroi D, Nocks A, Stamenkovic I. A single N-linked glycosylation site is implicated in the regulation of ligand recognition by the I-type lectins CD22 and CD33. J Biol Chem. 1996 Aug 2;271(31):18803–18809. [PubMed]

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