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THE CUTANEOUS LYMPHOCYTE ANTIGEN IS A SKIN LYMPHOCYTE HOMING RECEPTOR FOR THE VASCULAR LECTIN ENDOTHELIAL CELL-LEUKOCYTE ADHESION MOLECULE-1
Author(s): BERG EL, YOSHINO T, ROTT LS, ROBINSON MK, WARNOCK RA, KISHIMOTO TK, PICKER LJ, BUTCHER EC
Source: JOURNAL OF EXPERIMENTAL MEDICINE    Volume: 174    Issue: 6    Pages: 1461-1466    Published: DEC 1 1991  
Times Cited: 431     References: 26     
Abstract: 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 (sLe(x)) 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 sLe(x). The identification of a lymphocyte homing receptor for skin may permit novel approaches to the diagnosis and therapy of cutaneous and inflammatory disorders.
Document Type: Article
Language: English
Addresses:
1. STANFORD UNIV, DEPT PATHOL, IMMUNOL & VASC BIOL LAB, STANFORD, CA 94305 USA
2. STANFORD UNIV, CTR DIGEST DIS, STANFORD, CA 94305 USA
3. VET ADM MED CTR, CTR MOLEC BIOL MED, PALO ALTO, CA 94304 USA
Publisher: ROCKEFELLER UNIV PRESS, 222 E 70TH STREET, NEW YORK, NY 10021
Subject Category: Immunology; Medicine, Research & Experimental
IDS Number: GU644
ISSN: 0022-1007
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