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Phospholipase Cγ2 plays a role in TCR signal transduction and T cell selection. J Immunol 2012 Sep 01;189(5):2326-32

Date

07/28/2012

Pubmed ID

22837484

Pubmed Central ID

PMC3528184

DOI

10.4049/jimmunol.1103458

Scopus ID

2-s2.0-84865414173   11 Citations

Abstract

One of the important signaling events following TCR engagement is activation of phospholipase Cγ (PLCγ). PLCγ has two isoforms, PLCγ1 and PLCγ2. It is known that PLCγ1 is important for TCR signaling and TCR-mediated T cell selection and functions, whereas PLCγ2 is critical for BCR signal transduction and BCR-mediated B cell maturation and functions. In this study, we report that PLCγ2 was expressed in primary T cells, and became associated with linker for activated T cells and Src homology 2-domain containing leukocyte protein of 76 kDa and activated upon TCR stimulation. PLCγ1/PLCγ2 double-deficient T cells displayed further block from CD4 and CD8 double-positive to single-positive transition compared with PLCγ1 single-deficient T cells. TCR-mediated proliferation was further impaired in PLCγ1/PLCγ2 double-deficient T cells compared with PLCγ1 single-deficient T cells. TCR-mediated signal transduction, including Ca²⁺ mobilization and Erk activation, was further impaired in PLCγ1/PLCγ2 double-deficient relative to PLCγ1 single-deficient T cells. In addition, in HY TCR transgenic mouse model, thymic positive and negative selections were reduced in PLCγ1 heterozygous- and PLCγ2 homozygous-deficient (PLCγ1⁺/⁻PLCγ2⁻/⁻) relative to wild-type, PLCγ2 single-deficient (PLCγ2⁻/⁻), or PLCγ1 heterozygous-deficient (PLCγ1⁺/⁻) mice. Taken together, these data demonstrate that PLCγ2 participates in TCR signal transduction and plays a role in T cell selection.

Author List

Fu G, Chen Y, Schuman J, Wang D, Wen R

Authors

Demin Wang PhD Assistant Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Renren Wen PhD Associate Investigator in the Blood Research Institute department at BloodCenter of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Cell Differentiation
Cells, Cultured
Female
Male
Mice
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Phospholipase C gamma
Primary Cell Culture
Receptors, Antigen, T-Cell
Signal Transduction
Thymus Gland
jenkins-FCD Prod-469 c3fc8ab87196149f9b23743c01b947d47e7319e5