Normal Development and Function of T Cells in Proline Rich 7 (Prr7) Deficient Mice.

Matous Hrdinka,Ales Drobek,Kritika Sudan,Sissy Just,Dirk Reinhold,Michael R Kreutz,Burkhart Schraven,Bryen A Jordan,Patricia Gintschel,Dirk Schlüter,Ondrej Stepanek

doi:10.1371/journal.pone.0162863

Abstract

Transmembrane adaptor proteins (TRAPs) are important organisers for the transduction of immunoreceptor-mediated signals. Prr7 is a TRAP that regulates T cell receptor (TCR) signalling and potently induces cell death when overexpressed in human Jurkat T cells. Whether endogenous Prr7 has a similar functional role is currently unknown. To address this issue, we analysed the development and function of the immune system in Prr7 knockout mice. We found that loss of Prr7 partially impairs development of single positive CD4+ T cells in the thymus but has no effect on the development of other T cell subpopulations, B cells, NK cells, or NKT cells. Moreover, Prr7 does not affect the TCR signalling pathway as T cells derived from Prr7 knockout and wild-type animals and stimulated in vitro express the same levels of the activation marker CD69, and retain their ability to proliferate and activate induced cell death programs. Importantly, Prr7 knockout mice retained the capacity to mount a protective immune response when challenged with Listeria monocytogenes infection in vivo. In addition, T cell effector functions (activation, migration, and reactivation) were normal following induction of experimental autoimmune encephalomyelitis (EAE) in Prr7 knockout mice. Collectively, our work shows that loss of Prr7 does not result in a major immune system phenotype and suggests that Prr7 has a dispensable function for TCR signalling.

Highlights

Activation of lymphocytes by antigens is the key process of adaptive immune responses
Proline Rich 7 (Prr7) is expressed in mouse immune organs and T cells
Since the expression of Prr7 in mouse immune system has not been studied, we first analysed the mRNA levels of Prr7 in the thymus, spleen, lymph nodes, and T cells purified from lymph nodes of wild-type C57BL/6 mice

Summary

Introduction

Activation of lymphocytes by antigens is the key process of adaptive immune responses. A complex interplay of proteins in the signalling pathways originating from activated immune receptors (e.g. T cell receptor, TCR; B cell receptor, BCR; Fc receptors, FcRs) is required at specific stages of lymphocyte activation. TRAPs regulate intracellular signalling via diverse motifs SH2-, SH3- and PDZligands) within their intracellular domains. There are 14 members of the TRAP family (LAT, PAG/Cbp, NTAL/LAB, LIME, SIT1, TRIM, LAX, TCRz, FcRγ, DAP10, DAP12, PRR7, SCIMP, LST1/A) [3]. LAT, the archetypal and most studied member of the TRAP family, is recruited to the TCR complex upon TCR stimulation and is indispensable for correct T cell development and optimal TCR signalling during adaptive immune responses [4, 5]. The functional importance of LAT is underscored by the severe phenotype of LAT-deficient mice, which are completely devoid of peripheral T cells [6]

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