Protocadherin-18 is a novel differentiation marker and an inhibitory signaling receptor for CD8+ effector memory T cells.

PloS One
Edwin J Vazquez-CintronA B Frey

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 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(hi)CD127(+)) coincident with conversion into effector memory cells (CD44(+)CD62L(lo)CD127(+)). 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.

References

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Citations

Jan 8, 2016·Translational Research : the Journal of Laboratory and Clinical Medicine·Lili GaoJianfeng Zhou
Jan 16, 2013·Gene Expression Patterns : GEP·Juntang LinChristoph Redies
Apr 17, 2008·Biochemical and Biophysical Research Communications·Arun T Pores-FernandoAdam Zweifach
Sep 26, 2019·Frontiers in Neuroscience·Keiko Morimoto, Kazunori Nakajima

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Datasets Mentioned

BETA
GSE34618

Methods Mentioned

BETA
transfection
immuneprecipitation
PCR
FACS
flow cytometry
gene array
transfect

Software Mentioned

SDS
GeneSpring
EXPANDER
GO
BLAST
EASE

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