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- Title
Protocadherin-18 Is a Novel Differentiation Marker and an Inhibitory Signaling Receptor for CD8<sup>+</sup> Effector Memory T Cells.
- Authors
Vazquez-Cintron, Edwin J.; Monu, Ngozi R.; Burns, Jeremy C.; Blum, Roy; Chen, Gregory; Lopez, Peter; Ma, Jennifer; Radoja, Sasa; Frey, Alan B.
- Abstract
CD8+ tumor infiltrating T cells (TIL) lack effector-phase functions due to defective proximal TCR-mediated signaling previously shown to result from inactivation of p56lck kinase. We identify a novel interacting partner for p56lck 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+CD62LhiCD127+) coincident with conversion into effector memory cells (CD44+CD62LloCD127+). 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.
- Publication
PLoS ONE, 2012, Vol 7, Issue 5, p1
- ISSN
1932-6203
- Publication type
Academic Journal
- DOI
10.1371/journal.pone.0036101