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

Ellen L. Berg, Tadashi Yoshino, Lusijah S. Rott, Martyn K. Robinson, R. Aaron Warnock, Takashi K. Kishimoto, Louis Picker, Eugene C. Butcher

Research output: Contribution to journalArticle

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Abstract

A skin-associated popul.ation 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- 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 (NeuAcα2-3Galβ1-4[Fucα1-3]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 NeuAcα2-3Gal 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.

Original languageEnglish (US)
Pages (from-to)1461-1466
Number of pages6
JournalJournal of Experimental Medicine
Volume174
Issue number6
StatePublished - Dec 1 1991
Externally publishedYes

Fingerprint

Lymphocyte Homing Receptors
Cell Adhesion Molecules
Lectins
Endothelial Cells
Lymphocytes
Antigens
Skin
E-Selectin
T-Lymphocytes
Neuraminidase
Fucose
Acetylglucosamine

ASJC Scopus subject areas

  • Immunology

Cite this

Berg, E. L., Yoshino, T., Rott, L. S., Robinson, M. K., Warnock, R. A., Kishimoto, T. K., ... Butcher, E. C. (1991). The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule. Journal of Experimental Medicine, 174(6), 1461-1466.

The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule. / Berg, Ellen L.; Yoshino, Tadashi; Rott, Lusijah S.; Robinson, Martyn K.; Warnock, R. Aaron; Kishimoto, Takashi K.; Picker, Louis; Butcher, Eugene C.

In: Journal of Experimental Medicine, Vol. 174, No. 6, 01.12.1991, p. 1461-1466.

Research output: Contribution to journalArticle

Berg, EL, Yoshino, T, Rott, LS, Robinson, MK, Warnock, RA, Kishimoto, TK, Picker, L & Butcher, EC 1991, 'The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule', Journal of Experimental Medicine, vol. 174, no. 6, pp. 1461-1466.
Berg, Ellen L. ; Yoshino, Tadashi ; Rott, Lusijah S. ; Robinson, Martyn K. ; Warnock, R. Aaron ; Kishimoto, Takashi K. ; Picker, Louis ; Butcher, Eugene C. / The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule. In: Journal of Experimental Medicine. 1991 ; Vol. 174, No. 6. pp. 1461-1466.
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abstract = "A skin-associated popul.ation 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- 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 (NeuAcα2-3Galβ1-4[Fucα1-3]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 NeuAcα2-3Gal 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.",
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