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
Decoupling peptide binding from T cell receptor recognition with engineered chimeric MHC-I molecules
Georgia Papadaki,Omar Al Ani,Tyler J. Florio,Michael C. Young,Julia N Danon,Yi Sun,Devin Charles Dersh,Nikolaos G. Sgourakis +7 more
TL;DR: In this paper , a fixed-backbone computational design approach for engineering synthetic molecules that combine peptide binding and TCR recognition surfaces from existing HLA allotypes is presented, which underscore a novel, structure-guided platform for developing synthetic HLA molecules with desired properties as screening probes for peptide-centric interactions with TCRs and other therapeutic modalities.
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