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3429 CD44 and PSGL-1 Collaborate in Controlling the Migration of Human Activated T-Cells

Lymphocytes, Lymphocyte Activation and Immunodeficiency, including HIV and Other Infections
Program: Oral and Poster Abstracts
Session: 203. Lymphocytes, Lymphocyte Activation and Immunodeficiency, including HIV and Other Infections: Poster III
Monday, December 7, 2015, 6:00 PM-8:00 PM
Hall A, Level 2 (Orange County Convention Center)

Amal J. Ali1*, Jasmeen S. Merzaban, PhD2 and Ayman F. Abuelela2*

1BIOLOGICAL AND ENVIRONMENTAL SCIENCE AND ENGINEERING, King Abdullah University of Science and Technology, Thuwal, Saudi Arabia
2Division of Biological and Environmental Sciences & Engineering, King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia

Selectins play a central role in the trafficking of activated T cells by mediating tethering and rolling on vascular endothelium, acting as a beacon to help navigate them to the site of infection. Here we present a comprehensive binding and in vitro functional analysis of E-selectin ligands expressed on human activated T cells. Using a mass-spectrometric approach we identified a number of glycoproteins that may act as physiological E-selectin ligands on human activated T cells and focused on comparing the role the previously identified well-known E-selectin ligands, PSGL-1 (P-selectin glycoprotein ligand 1) to the newly identified ligand CD44. We show that CD44 from human activated CD4+ and CD8+ T cells binds E-selectin, and that immobilized CD44 mediates tethering and rolling of E-selectin expressing CHO cells via sialylated N-linked glycans. By knocking down CD44 and/or PSGL-1 in primary human activated T cells, our data demonstrate for the first time that CD44 is essential for mediating the rolling over E-selectin and thereby cooperates with PSGL-1 as a major E-selectin ligand on human activated T cells. This has major implications in the development of targeted therapies to combat inflammatory diseases and in transplantation settings.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH