The very first event in T cell receptor (TCR)/CD3 complex activation is the phosphorylation of the cytoplasmic tails of CD3ζ by the tyrosine kinase Lck. This allows for the recruitment of the kinase ZAP70, which phosphorylates a number of downstream mediators and effectors to amplify TCR/CD3 signaling.
Adaptor molecules couple the TCR/CD3 to a variety of signaling molecules involved in T cell activation and as such play a key role as signal amplifiers. Adaptors include both transmembrane and cytosolic molecules, such as LAT, SLP-76, GRB2, SHC, and Gads. While some adaptor molecules, like TSAd and Nck, participate in proximal TCR/CD3 signaling by recruiting Lck, other adaptors, such as PAG and SIT, negatively regulate TCR signaling, thereby contributing to signal termination.
In the past decade, TCR signaling has been heavily investigated for exploitation in cancer immunotherapy through approaches involving CAR T cells or other engineered T cells such as TRuC T cells and TCR-T cells. Adaptor proteins have fundamental roles in the fine-tuning of the tightly controlled intricate process of TCR/CD3 signaling both in T cell homeostasis and immune responses. Harnessing their signal modulating properties may help develop better cancer immunotherapies. Additionally, adaptor molecules are among the components of the TCR signaling cascade being investigated for their implication in pathological conditions including autoimmunity and hematologic malignancies and some adaptor molecules have been identified as therapeutic targets to treat or alleviate those conditions.
We welcome the submission of Reviews, Mini-Reviews, and Original Research articles that provide new insights into the following areas involving the adaptor proteins found in T cells:
1. Their role in proximal and distal TCR signaling
2. Their role in thymocyte development and T cell differentiation
3. Their participation in T cell signalosomes
4. Their role in autoimmunity and their exploitation as drug targets
5. Their role in T cell therapy against cancers
6. Their regulation by cytokines and other signaling mediators
This Research Topic is the second volume of the “Community Series in Adaptor Molecules in T Cell Signaling”. Please see the first volume
here"