RT Journal Article
SR Electronic
T1 Activated CD8 T cells express two distinct P-Selectin Ligands
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 167957
DO 10.1101/167957
A1 Douglas A. Carlow
A1 Michelle C. Tra
A1 Hermann J. Ziltener
YR 2017
UL http://biorxiv.org/content/early/2017/07/24/167957.abstract
AB P-selectin (PSel) expressed on activated endothelia and platelets supports the recruitment of leukocytes expressing PSel ligand (PSelL) to sites of inflammation. While monitoring PSelL expression on activated CD8+ T cells (Tact) in adoptive transfer models, we observed two distinct PSelL on responding donor cells, the canonical cell-intrinsic PSelL PSGL1 and a second undocumented PSelL we provisionally name PSL2. PSL2 is unusual among selectin ligands expressed on leukocytes in that it is externally sourced (cell-extrinsic) and loaded onto L-selectin (LSel) expressed by Tact but not onto LSel of resting naïve CD8+ T cells. PSL2 is a ligand for both PSel and LSel and can engage both simultaneously, physically bridging the two selectins. PSL2 can mediate PSel-dependent adherence of Tact to immobilized PSel-hIgG chimera or to activated platelets, either independently or cooperatively with PSGL1. When both PSGL1 and PSL2 were absent from the surface of Tact, no significant residual PSelL activity was detected. PSL2 expression is highest on Tact responding in peripheral lymph nodes and low on Tact responding in spleen suggesting that the original source of PSL2 is high endothelial venules, cells known to produce LSelL. We conclude that two PSel ligands, PSGL1 and PSL2, are present on primary in vivo generated Tact; both can cooperate in physical cell adhesion to PSel-bearing substrates and would likely deliver distinct signals known to be transmitted through PSGL1 and LSel respectively and relevant to successful recruitment.HighlightsCD8+ T cells activated in lymph nodes express two P-selectin ligands - PSGL1 and PSL2PSL2 is cell-extrinsic and loaded onto L-selectin on activated CD8+ T cellsThe L-selectin/PSL2 complex co-operates with PSGL1 for adherence to P-selectinPSL2 draws L-selectin into engagement with P-selectin-bearing substrateseTOC blurb Carlow et al. show that activated CD8+ T cells express both the canonical cell-intrinsic P-selectin ligand PSGL-1 and a second cell-extrinsic P-selectin ligand, PSL2. PSL2 docks on L-selectin and cooperates with PSGL1 for adhesion to substrates bearing P-selectin thereby physically bridging P-selectin and L-selectin.