T Cell Activation

Abstract

This year marks the twenty-fifth anniversary of the first Annual Review in Immunology article to describe features of the T cell antigen receptor (TCR). In celebration of this anniversary, we begin with a brief introduction outlining the chronology of the earliest studies that established the basic paradigm for how the engaged TCR transduces its signals. This review continues with a description of the current state of our understanding of TCR signaling, as well as a summary of recent findings examining other key aspects of T cell activation including crosstalk between the TCR and integrins, the role of costimulatory molecules, and how signals may negatively regulate T cell function.

Integrins as therapeutic targets: lessons and opportunities

“…Thus, embryonic development 16 and angiogenesis 17 are critically dependent on integrins, as is the immune system 18 in which immune cell attachment is necessary for normal function (see below).…”

“…Both β 1 and β 2 integrins are important in immune function where they play essential roles in localizing the immune response to the site of inflammation 11 and a defect in β 2 integrins leads to life-threatening immune dysfunction (leucocyte adhesion deficiency, LAD) 32 . Engagement of the T-cell receptor and subsequent inside-out signalling leads to activation of T-cell integrins 18 .…”

P21‐activated kinase 2 is essential in maintenance of peripheral Foxp3+ regulatory T cells

“…Once T cells are activated by TCR/CD28 co‐stimulation, the cells produce great amounts of IL‐2 and increased high‐affinity IL‐2 receptor, CD25. IL‐2/IL‐2R signalling provides a strong proliferation signal to T cells 7, 26. Expression of IL‐2 and CD25 were significantly decreased even upon TCR/CD28 stimulation in Pak2 KO CD4 T cells in vitro , and these defects were only partially rescued by exogenous IL‐2.…”

“…Among these signalling pathways, Rho family GTPases regulate actin cytoskeleton rearrangement associated with T‐cell activation, while mitogen‐activated protein kinase and mammalian target of rapamycin (mTOR) play a key role in T‐cell proliferation. Once T cells are activated, they increase expression of CD25, CD69 and CD40L, and produce cytokines such as interleukin‐2 (IL‐2), which subsequently provide additional proliferative signals to T cells 7. TCR stimulation of naive CD4 T cells in the presence of various cytokines provides signals differentiating them into specialized effector cells such as T helper type 1 (Th1) [with IL‐12 or interferon‐ γ (IFN‐ γ )], Th2 (with IL‐4), Th17 [with IL‐6 and transforming growth factor‐ β (TGF‐ β )] and induced regulatory T (iTreg) cells (with IL‐2 and TGF‐ β ) 1, 8.…”

Transcriptome analysis of soiny mullet (Liza haematocheila) spleen in response to Streptococcus dysgalactiae

“…T cell activation depends on the binding of TCR with antigens that are presented by major (MHC) molecules [41]. Upon activation, T cells can assist in activating other cells or carry out cytolytic attacks to eliminate the antigens.…”