Search tips
Search criteria 


Logo of jexpmedHomeThe Rockefeller University PressEditorsContactInstructions for AuthorsThis issue
J Exp Med. 1991 December 1; 174(6): 1461–1466.
PMCID: PMC2119052

The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule 1


A skin-associated population of memory T lymphocytes, defined by expression of the cutaneous lymphocyte antigen (CLA), binds selectively and avidly to the vascular lectin endothelial cell-leukocyte adhesion molecule 1 (ELAM-1), an interaction that may be involved in targeting of CLA+ T cells to cutaneous sites of chronic inflammation. Here we present evidence that CLA itself is the (or a) lymphocyte homing receptor for ELAM-1. Antigen isolated with anti-CLA monoclonal antibody HECA-452 from human tonsillar lysates avidly binds ELAM-1 transfected mouse cells. Anti-CLA antibody blocks T lymphocyte binding to ELAM-1 transfectants. HECA-452 and ELAM-1 binding to lymphocytes or to isolated tonsillar HECA-452 antigen is abrogated by neuraminidase treatment implying a prominent role for sialic acid in CLA structure and function. The dominant form of CLA on T cells is immunologically distinct from the major neutrophil ELAM-1 ligand, the sialyl Lewis x (sLex) antigen (NeuAc alpha 2-3Gal beta 1-4[Fuc alpha 1-3]GlcNAc), which is absent, weakly expressed, or masked on T cells. However, neuraminidase treatment of CLA+ T cells, but not of CLA- T cells, reveals Lewis x (CD15) structures. In combination with the known requirement for terminal NeuAc alpha 2-3Gal and fucose residues attached to N-acetylglucosamine for ELAM-1 and HECA-452 binding, this finding suggests that CLA may comprise an additionally sialylated or otherwise modified form of sLex. The identification of a lymphocyte homing receptor for skin may permit novel approaches to the diagnosis and therapy of cutaneous and inflammatory disorders.

Full Text

The Full Text of this article is available as a PDF (700K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Picker LJ, Michie SA, Rott LS, Butcher EC. A unique phenotype of skin-associated lymphocytes in humans. Preferential expression of the HECA-452 epitope by benign and malignant T cells at cutaneous sites. Am J Pathol. 1990 May;136(5):1053–1068. [PubMed]
  • Picker LJ, Terstappen LW, Rott LS, Streeter PR, Stein H, Butcher EC. Differential expression of homing-associated adhesion molecules by T cell subsets in man. J Immunol. 1990 Nov 15;145(10):3247–3255. [PubMed]
  • Picker LJ, Kishimoto TK, Smith CW, Warnock RA, Butcher EC. ELAM-1 is an adhesion molecule for skin-homing T cells. Nature. 1991 Feb 28;349(6312):796–799. [PubMed]
  • Berg EL, Robinson MK, Warnock RA, Butcher EC. The human peripheral lymph node vascular addressin is a ligand for LECAM-1, the peripheral lymph node homing receptor. J Cell Biol. 1991 Jul;114(2):343–349. [PMC free article] [PubMed]
  • Jalkanen ST, Bargatze RF, Herron LR, Butcher EC. A lymphoid cell surface glycoprotein involved in endothelial cell recognition and lymphocyte homing in man. Eur J Immunol. 1986 Oct;16(10):1195–1202. [PubMed]
  • Berg EL, Robinson MK, Mansson O, Butcher EC, Magnani JL. A carbohydrate domain common to both sialyl Le(a) and sialyl Le(X) is recognized by the endothelial cell leukocyte adhesion molecule ELAM-1. J Biol Chem. 1991 Aug 15;266(23):14869–14872. [PubMed]
  • Coffman RL, Weissman IL. A monoclonal antibody that recognizes B cells and B cell precursors in mice. J Exp Med. 1981 Feb 1;153(2):269–279. [PMC free article] [PubMed]
  • Kishimoto TK, Jutila MA, Butcher EC. Identification of a human peripheral lymph node homing receptor: a rapidly down-regulated adhesion molecule. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2244–2248. [PubMed]
  • Wood GS, Link M, Warnke RA, Dilley J, Levy R. Pan-leukocyte monoclonal antibody L3B12. Characterization and application to research and diagnostic problems. Am J Clin Pathol. 1984 Feb;81(2):176–183. [PubMed]
  • Streeter PR, Rouse BT, Butcher EC. Immunohistologic and functional characterization of a vascular addressin involved in lymphocyte homing into peripheral lymph nodes. J Cell Biol. 1988 Nov;107(5):1853–1862. [PMC free article] [PubMed]
  • Fukushima K, Hirota M, Terasaki PI, Wakisaka A, Togashi H, Chia D, Suyama N, Fukushi Y, Nudelman E, Hakomori S. Characterization of sialosylated Lewisx as a new tumor-associated antigen. Cancer Res. 1984 Nov;44(11):5279–5285. [PubMed]
  • Walz G, Aruffo A, Kolanus W, Bevilacqua M, Seed B. Recognition by ELAM-1 of the sialyl-Lex determinant on myeloid and tumor cells. Science. 1990 Nov 23;250(4984):1132–1135. [PubMed]
  • Lowe JB, Stoolman LM, Nair RP, Larsen RD, Berhend TL, Marks RM. ELAM-1--dependent cell adhesion to vascular endothelium determined by a transfected human fucosyltransferase cDNA. Cell. 1990 Nov 2;63(3):475–484. [PubMed]
  • Phillips ML, Nudelman E, Gaeta FC, Perez M, Singhal AK, Hakomori S, Paulson JC. ELAM-1 mediates cell adhesion by recognition of a carbohydrate ligand, sialyl-Lex. Science. 1990 Nov 23;250(4984):1130–1132. [PubMed]
  • Fukuda M, Spooncer E, Oates JE, Dell A, Klock JC. Structure of sialylated fucosyl lactosaminoglycan isolated from human granulocytes. J Biol Chem. 1984 Sep 10;259(17):10925–10935. [PubMed]
  • Springer TA, Lasky LA. Cell adhesion. Sticky sugars for selectins. Nature. 1991 Jan 17;349(6306):196–197. [PubMed]
  • Mackay CR. Lymphocyte homing. Skin-seeking memory T cells. Nature. 1991 Feb 28;349(6312):737–738. [PubMed]
  • Ohmori K, Yoneda T, Ishihara G, Shigeta K, Hirashima K, Kanai M, Itai S, Sasaoki T, Arii S, Arita H, et al. Sialyl SSEA-1 antigen as a carbohydrate marker of human natural killer cells and immature lymphoid cells. Blood. 1989 Jul;74(1):255–261. [PubMed]
  • Fournet B, Montreuil J, Strecker G, Dorland L, Haverkamp J, Vliegenthart FG, Binette JP, Schmid K. Determination of the primary structures of 16 asialo-carbohydrate units derived from human plasma alpha 1-acid glycoprotein by 360-MHZ 1H NMR spectroscopy and permethylation analysis. Biochemistry. 1978 Nov 28;17(24):5206–5214. [PubMed]
  • Goelz SE, Hession C, Goff D, Griffiths B, Tizard R, Newman B, Chi-Rosso G, Lobb R. ELFT: a gene that directs the expression of an ELAM-1 ligand. Cell. 1990 Dec 21;63(6):1349–1356. [PubMed]
  • Lewinsohn DM, Bargatze RF, Butcher EC. Leukocyte-endothelial cell recognition: evidence of a common molecular mechanism shared by neutrophils, lymphocytes, and other leukocytes. J Immunol. 1987 Jun 15;138(12):4313–4321. [PubMed]
  • Kishimoto TK, Jutila MA, Berg EL, Butcher EC. Neutrophil Mac-1 and MEL-14 adhesion proteins inversely regulated by chemotactic factors. Science. 1989 Sep 15;245(4923):1238–1241. [PubMed]
  • Jutila MA, Rott L, Berg EL, Butcher EC. Function and regulation of the neutrophil MEL-14 antigen in vivo: comparison with LFA-1 and MAC-1. J Immunol. 1989 Nov 15;143(10):3318–3324. [PubMed]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press