Journal Article10.1146/ANNUREV.IMMUNOL.23.021704.115658
How TCRs Bind MHCs, Peptides, and Coreceptors
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TL;DR: The structural basis for MHC restriction and signaling remains elusive as no structural features that define a common binding mode or signaling mechanism have yet been gleaned from the current set of TCR/pMHC complexes.
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Abstract: Since the first crystal structure determinations of alphabeta T cell receptors (TCRs) bound to class I MHC-peptide (pMHC) antigens in 1996, a sizable database of 24 class I and class II TCR/pMHC complexes has been accumulated that now defines a substantial degree of structural variability in TCR/pMHC recognition. Recent determination of free and bound gammadelta TCR structures has enabled comparisons of the modes of antigen recognition by alphabeta and gammadelta T cells and antibodies. Crystal structures of TCR accessory (CD4, CD8) and coreceptor molecules (CD3epsilondelta, CD3epsilongamma) have further advanced our structural understanding of most of the components that constitute the TCR signaling complex. Despite all these efforts, the structural basis for MHC restriction and signaling remains elusive as no structural features that define a common binding mode or signaling mechanism have yet been gleaned from the current set of TCR/pMHC complexes. Notwithstanding, the impressive array of self, foreign (microbial), and autoimmune TCR complexes have uncovered the diverse ways in which antigens can be specifically recognized by TCRs.
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Citations
Primary T cell immunodeficiencies associated with disturbed proximal T cell receptor signalling caused by human autosomal recessive LCK, ZAP-70 and ITK-mutations : Immunodéficiences primaires des cellules T associées avec une signalisation proximale du récepteur à l’antigène des cellules T perturbée et causées par des mutations autosomiques récessives humaines de LCK, ZAP-70 et ITK
Fabian Hauck
- 01 Jan 2013
TL;DR: This doctoral thesis provides detailed clinical, immunological and biochemical analyses especially of TCR:CD3:ζ-signalling and compares the findings to the well-established Lck-/-, Zap-70-/- and Itk-/- murine models.
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Transcriptional Regulation of T Cell Metabolism Reprograming
TL;DR: This review describes how signaling pathways of TCR and cytokines regulate metabolic reprograming and then focuses on transcription factors that control metabolic pathways and outcomes of T cell immune responses.
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