The monoclonal antibody CHO-131 identifies a subset of cutaneous lymphocyte-associated antigen T cells enriched in P-selectin-binding cells

J Immunol. 2006 Oct 1;177(7):4742-8. doi: 10.4049/jimmunol.177.7.4742.

Abstract

T cells use the vascular adhesion molecules E- and P-selectin to enter inflamed skin. Previous studies have indicated the possibility for diversity in the synthesis of E- and P-selectin glycan ligands by activated T cells due to their different requirements for the O-glycan branching enzyme core 2 beta1,6-N-acetylglucosaminyltransferase I and its independent regulation. It is known that T cell staining by the mAb HECA-452 (referred to as cutaneous lymphocyte-associated Ag (CLA) T cells) correlates with E-selectin binding, yet whether these cells uniformly bind P-selectin is less clear. The mAb CHO-131 and P-selectin binding require a glycan moiety consisting of a sialylated and fucosylated oligosaccharide properly positioned on a core-2 O-glycan. Interestingly, CHO-131 stains a subset of CLA(+) T cells. A direct comparison of the selectin binding capacity of CHO-131(+) and CHO-131(-) CLA(+) T cells revealed a significantly greater P-selectin, but not E-selectin, binding activity by the former subset. Based on the expression of homing and central and effector memory cell markers, CHO-131(+) and CHO-131(-) CLA(+) T cells have an overlapping skin-tropic and memory phenotype. CHO-131(+) T cells were considerably enriched in psoriatic skin, yet, unlike the peripheral blood of healthy individuals, HECA-452 and CHO-131 stained a similar proportion of T cells in the cutaneous lesions, indicating an accumulation advantage by CHO-131(+) T cells. We conclude that the CHO-131(+)CLA(+) T cell subset is enriched in P-selectin binding cells. These findings should provide new insights into the regulation and function of skin homing T cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Monoclonal / immunology*
  • E-Selectin / immunology
  • E-Selectin / metabolism
  • Epitopes, T-Lymphocyte / immunology
  • Flow Cytometry
  • Fluorescent Antibody Technique
  • Humans
  • Immunologic Memory
  • Lymphocyte Activation / immunology
  • Lymphocyte Subsets / immunology*
  • Lymphocyte Subsets / metabolism
  • Membrane Glycoproteins / immunology*
  • Oligosaccharides / immunology
  • P-Selectin / metabolism*
  • Psoriasis / immunology
  • Sialyl Lewis X Antigen
  • Skin / cytology
  • Skin / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Antibodies, Monoclonal
  • E-Selectin
  • Epitopes, T-Lymphocyte
  • Membrane Glycoproteins
  • Oligosaccharides
  • P-Selectin
  • Sialyl Lewis X Antigen