Protocadherin-18 Is a Novel Differentiation Marker and an Inhibitory Signaling Receptor for CD8+ Effector Memory T Cells

by Edwin J. Vazquez-Cintron, Ngozi R. Monu, Jeremy C. Burns, Roy Blum, Gregory Chen, Peter Lopez, Jennifer Ma, Sasa Radoja, Alan B. Frey

CD8⁺ tumor infiltrating T cells (TIL) lack effector-phase functions due to defective proximal TCR-mediated signaling previously shown to result from inactivation of p56^lck kinase. We identify a novel interacting partner for p56^lck in nonlytic TIL, Protocadherin-18 (‘pcdh18’), and show that pcdh18 is transcribed upon in vitro or in vivo activation of all CD8⁺ central memory T cells (CD44⁺CD62L^hiCD127⁺) coincident with conversion into effector memory cells (CD44⁺CD62L^loCD127⁺). Expression of pcdh18 in primary CD8⁺ effector cells induces the phenotype of nonlytic TIL: defective proximal TCR signaling, cytokine secretion, and cytolysis, and enhanced AICD. pcdh18 contains a motif (centered at Y842) shared with src kinases (QGQYQP) that is required for the inhibitory phenotype. Thus, pcdh18 is a novel activation marker of CD8⁺ memory T cells that can function as an inhibitory signaling receptor and restrict the effector phase.

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Protocadherin-18 Is a Novel Differentiation Marker and an Inhibitory Signaling Receptor for CD8+ Effector Memory T Cells
Syndicated from:PLoS ONE

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