Fine-tuning T cell receptor signaling to control T cell development

Recent Advances in T Cell Signaling in Aging

The immune system of mammalian organisms undergoes alterations that may account for an increased susceptibility to certain infections, autoimmune diseases, or malignancies. Well characterized are age related defect in T cell functions and cell mediated immunity. Although it is well established that the functional properties of T cells decrease with age, its biochemical and molecular nature is...

Altered T cell receptor signaling and disrupted T cell development in mice lacking Itk.

Itk is a T cell protein tyrosine kinase (PTK) that, along with Btk and Tec, belongs to a family of cytoplasmic PTKs with N-terminal pleckstrin homology domains. Btk plays a critical role in B lymphocyte development. To determine whether Itk has an analogous role in T lymphocytes, we used gene targeting to prepare mice lacking expression of Itk. Such animals had decreased numbers of mature thymo...

Sustained signaling leading to T cell activation results from prolonged T cell receptor occupancy. Role of T cell actin cytoskeleton

Using antigen-specific T cell clones and peptide-pulsed antigen-presenting cells (APCs) we investigated the mechanisms that lead to sustained signaling, known to be required for activation of effector function. Four lines of evidence indicate that the T cell actin cytoskeleton plays a crucial role in T cell activation by antigen-pulsed APCs, but is not required when T cell receptor (TCR) is cro...

The T-cell-receptor signaling network.

T-cell-receptor (TCR) signaling in response to antigen recognition has a central role in the adaptive immune response. Furthermore, the comprehensive nature of the TCR signaling network is such that it has become a model system for complex cellular responses ranging from gene regulation to cytoskeletal remodeling. Over the past five years, our understanding of TCR signaling has evolved on a num...

Viral modulation of T-cell receptor signaling.