Cutaneous lymphocyte antigen is a specialized form of PSGL-1 expressed on skin-homing T cells.
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 lymphoma. 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 skin. CLA is defined by both its reactivity with a unique monoclonal antibody, HECA-452, and its activity as a ligand for E-selectin, 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.
Fuhlbrigge
R C
RC
Harvard Skin Disease Research Center, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA.
Kieffer
J D
JD
Armerding
D
D
Kupper
T S
TS
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007156:Immunologic Memory; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000737:chemistry; D011499:Protein Processing, Post-Translational; D016201:Receptors, Lymphocyte Homing / Q000096:biosynthesis* / Q000737:chemistry; D012867:Skin / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; D000951:Antigens, Neoplasm; C063419:CTAGE1 protein, human; D016895:Culture Media, Serum-Free; D018984:Epitopes, T-Lymphocyte; D008562:Membrane Glycoproteins; C084882:P-selectin ligand protein; D016201:Receptors, Lymphocyte Homing