CD43 is a ligand for E-selectin on CLA+ human T cells

Area of Science:

• Immunology
• Cell Biology
• Glycobiology

Background:

• T-cell recruitment to tissues is crucial for immune surveillance and inflammatory skin diseases like psoriasis.
• Human T cells infiltrating skin express the cutaneous lymphocyte-associated antigen (CLA) epitope, primarily on PSGL-1.
• PSGL-1 mediates E-selectin and P-selectin ligand functions for T-cell adhesion.

Purpose of the Study:

• To investigate if CD43, a sialomucin on T cells, can be decorated with the CLA epitope.
• To determine if CLA-decorated CD43 functions as an E-selectin ligand.
• To identify novel T-cell ligands involved in skin homing and immune regulation.

Main Methods:

• Immunochemical analysis of CLA expression on T-cell surface proteins.
• Purification of CLA-positive CD43 glycoforms.
• In vitro shear flow assays to assess E-selectin and P-selectin binding.

Main Results:

• CD43 is identified as a novel carrier of the CLA epitope on human T cells.
• CLA on CD43 is specifically associated with a high-molecular-weight glycoform (125 kDa) with core-2-branched O-linked glycans.
• CLA+ CD43 mediates E-selectin-dependent tethering and rolling, but not P-selectin binding.

Conclusions:

• CD43 functions as an E-selectin ligand distinct from PSGL-1.
• This discovery expands the known mechanisms of T-cell trafficking into the skin.
• Targeting CLA+ CD43 offers a new strategy for modulating immune responses in cutaneous inflammation.