title: Protocadherin-18 is a novel differentiation marker and an inhibitory signaling receptor for CD8+ effector memory T cells.
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.
authors.affiliation: Department of Cell Biology, New York University Langone School of Medicine New York, New York, United States of America.
authors.forename: Edwin J
authors.initials: EJ
authors.lastname: Vazquez-Cintron
authors.forename: Ngozi R
authors.initials: NR
authors.lastname: Monu
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Burns
authors.forename: Roy
authors.initials: R
authors.lastname: Blum
authors.forename: Gregory
authors.initials: G
authors.lastname: Chen
authors.forename: Peter
authors.initials: P
authors.lastname: Lopez
authors.forename: Jennifer
authors.initials: J
authors.lastname: Ma
authors.forename: Sasa
authors.initials: S
authors.lastname: Radoja
authors.forename: Alan B
authors.initials: AB
authors.lastname: Frey
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism*; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000378:metabolism; D008297:Male; D051379:Mice
chemical_list: D015820:Cadherins