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Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells

Nature volume 389, pages 978–981 (1997)Cite this article

Abstract

T cells play a pathogenic role in many inflammatory and certain malignant skin diseases, including psoriasis, atopic and allergic contact dermatitis, and cutaneous T-cell lymphoma1,2,3,4,5,6. Memory T cells that infiltrate the skin express a unique skin-homing receptor called cutaneous lymphocyte-associated antigen (CLA), a carbohydrate epitope that facilitates the targeting of T cells to inflamed skin1,7,8. CLA is defined by both its reactivity with a unique monoclonal antibody, HECA-452, and its activity as a ligand for E-selectin2,9,10,11, but the structure of the protein component of CLA has not previously been defined. Here we report that CLA is an inducible carbohydrate modification of P-selectin glycoprotein ligand-1 (PSGL-1), a known surface glycoprotein that is expressed constitutively on all human peripheral-blood T cells. Cultured peripheral-blood T cells can be differentiated into CLA-bearing cells, which bind both E-selectin and P-selectin, or CLA-negative cells, which bind P-selectin but do not bind E-selectin, suggesting that there is independent regulation of selectin-binding phenotypes. We propose that differential post-translational modification of a single cell-surface receptor, PSGL-1, mediated by fucosyltransferase VII, serves as a mechanism for regulating tissue-specific homing of memory T cells.

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Figure 1: Expression of CLA, sLex and PSGL-1 by fresh and cultured PBMCs.
Figure 2: Tethering and rolling of fresh and cultured PBMCs on selectins in physiological shear flow.
Figure 3: Immunoblotting of peripheral-blood T-cell lysates.
Figure 4: Immunoblot of lysates exposed to enhanced reducing conditions.
Figure 5: Immunoblot of immunoprecipitated PSGL-1 with HECA-452.

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Acknowledgements

We thank L. Picker for the HECA-452 antibody, and G. Larsen for the soluble recombinant PSGL-1 and antibodies to PSGL-1. We acknowledge the NIAMS and NIAID, NIH for support of this work.

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Author notes

  1. Robert C. Fuhlbrigge, J. David Kieffer and Dieter Armerding: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Dermatology, Department of Medicine, Harvard Skin Disease Research Center, Brigham and Women's Hospital, 75 Francis Street, Boston, 02115, Massachusetts, USA

    Thomas S. Kupper

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  1. Robert C. Fuhlbrigge
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Correspondence to Thomas S. Kupper.

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Fuhlbrigge, R., Kieffer, J., Armerding, D. et al. Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells. Nature 389, 978–981 (1997). https://doi.org/10.1038/40166

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