Abstract
The T-cell receptor (TCR)-CD3 complex, expressed on T cells, determines the outcome of a T-cell response. It consists of the TCR-αβ heterodimer and the non-covalently associated signalling dimers of CD3εγ, CD3εδ and CD3ζζ. TCR-αβ binds specifically to a cognate peptide antigen bound to an MHC molecule, whereas the CD3 subunits transmit the signal into the cytosol to activate signalling events. Recruitment of proteins to specialized localizations is one mechanism to regulate activation and termination of signalling. In the last 25 years a large number of signalling molecules recruited to the TCR-CD3 complex upon antigen binding to TCR-αβ have been described. Here, we review knowledge about five of those interaction partners: Lck, ZAP-70, Nck, WASP and Numb. Some of these proteins have been targeted in the development of immunomodulatory drugs aiming to treat patients with autoimmune diseases and organ transplants.
Keywords:
T-cell activation; T-cell receptor-CD3 complex; protein-protein interaction; signal transduction.
© 2017 John Wiley & Sons Ltd.
Publication types
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Review
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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CD3 Complex / chemistry
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CD3 Complex / genetics
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CD3 Complex / metabolism
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Carrier Proteins / chemistry
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Carrier Proteins / genetics
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Carrier Proteins / metabolism*
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Humans
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / metabolism
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Membrane Proteins / metabolism
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Mutation
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Nerve Tissue Proteins / metabolism
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Oncogene Proteins / metabolism
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Protein Binding
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Protein Interaction Domains and Motifs
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Receptor-CD3 Complex, Antigen, T-Cell / chemistry
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Receptor-CD3 Complex, Antigen, T-Cell / metabolism*
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Receptors, Antigen, T-Cell / chemistry
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Receptors, Antigen, T-Cell / genetics
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Receptors, Antigen, T-Cell / metabolism
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Signal Transduction*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism*
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Wiskott-Aldrich Syndrome Protein / metabolism
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ZAP-70 Protein-Tyrosine Kinase / metabolism
Substances
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Adaptor Proteins, Signal Transducing
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CD3 Complex
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Carrier Proteins
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Membrane Proteins
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Nck protein
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Nerve Tissue Proteins
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NUMB protein, human
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Oncogene Proteins
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Receptor-CD3 Complex, Antigen, T-Cell
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Receptors, Antigen, T-Cell
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Wiskott-Aldrich Syndrome Protein
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Lymphocyte Specific Protein Tyrosine Kinase p56(lck)
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ZAP-70 Protein-Tyrosine Kinase