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

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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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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