Identification of cutaneous lymphocyte-associated antigen as sialyl 6-sulfo Lewis X, a selectin ligand expressed on a subset of skin-homing helper memory T cells

We previously identified the carbohydrate determinant sialyl 6-sulfo Lewis X (Lex) as the major L-selectin ligand on high endothelial venules of peripheral lymph nodes. In this study, we examined the distribution of the sialyl 6-sulfo Lex determinant among peripheral lymphocytes. The determinant was expressed on a subset of helper memory T and NK cells. The helper memory T cells expressing sialyl 6-sulfo Lex were CD45RObright+PSGL-1high+CCR4+L-selectin+CCR7+ but did not express α4β7 integrin or CCR9, indicating that they were the skin-homing population of central memory T cells. The T-cell subset significantly expressed mRNA for 6-sulfotransferase HEC-GlcNAc6ST and fucosyltransferase Fuc-T VII, responsible for the synthesis of sialyl 6-sulfo Lex. Characteristics of the T-cell population were similar to those previously described for cutaneous lymphocyte-associated antigen (CLA)–positive T cells defined by the HECA-452 or 2F3 antibody. The binding of the T-cell subset with the specific anti–sialyl 6-sulfo Lex antibody G152 was almost completely abrogated by HECA-452 or 2F3. Binding of recombinant E-, P-, and L-selectins to the T-cell subset was significantly inhibited by G152 and by HECA-452 antibodies. We propose that CLA, which is expressed without any activation stimuli on peripheral skin-homing helper memory T cells in healthy persons, is at least partly the sialyl 6-sulfo Lex determinant.