The goal of this proposal is to answer a number of fundamental questions regarding the structural basis for the recognition of peptide/MHC class I complexes by T cell receptors (TCRs). Are there general structural principles which govern TCR-MHC interactions? Are these similar for TCR recognition of self and foreign MHC? Does conformational change or induced fit play a role in TCR-MHC recognition and communication among members of the TCR/MHC/CD3/CD8 signalling complex? X-ray crystallography will be used to investigate the detailed molecular interactions between a TCR specific for different syngeneic and allogeneic peptide/MHC class I complexes in the presence and absence of CD3 and CD8 components.
The specific aims are to determine the structures of: (i) TCR-MHC syngeneic class I-peptide complexes, (ii) TCR-allogeneic class I-peptide complexes, (iii) TCR/MHC/CD8 ternary complexes, (iv) agonist and antagonist TCR-MHC complexes, and (v) extracellular CD3 chains and their complexes with TCR.
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| Collins, Bernard C; Nakahara, Hiro; Acharya, Sharmistha et al. (2017) Crystal structure of an anti-idiotype variable lymphocyte receptor. Acta Crystallogr F Struct Biol Commun 73:682-687 |
| Collins, Bernard C; Gunn, Robin J; McKitrick, Tanya R et al. (2017) Structural Insights into VLR Fine Specificity for Blood Group Carbohydrates. Structure 25:1667-1678.e4 |
| Das, Nabanita; Dewan, Varun; Grace, Peter M et al. (2016) HMGB1 Activates Proinflammatory Signaling via TLR5 Leading to Allodynia. Cell Rep 17:1128-1140 |
| Baranczak, Aleksandra; Liu, Yu; Connelly, Stephen et al. (2015) A fluorogenic aryl fluorosulfate for intraorganellar transthyretin imaging in living cells and in Caenorhabditis elegans. J Am Chem Soc 137:7404-14 |
| Lockner, Jonathan W; Eubanks, Lisa M; Choi, Jennifer L et al. (2015) Flagellin as carrier and adjuvant in cocaine vaccine development. Mol Pharm 12:653-62 |
| Jiménez-Dalmaroni, Maximiliano J; Radcliffe, Catherine M; Harvey, David J et al. (2015) Soluble human TLR2 ectodomain binds diacylglycerol from microbial lipopeptides and glycolipids. Innate Immun 21:175-93 |
| Grover, Rajesh K; Zhu, Xueyong; Nieusma, Travis et al. (2014) A structurally distinct human mycoplasma protein that generically blocks antigen-antibody union. Science 343:656-661 |
| Collins, Bernard; Wilson, Ian A (2014) Crystal structure of the C-terminal domain of mouse TLR9. Proteins 82:2874-8 |
| Myung, Nojoon; Connelly, Stephen; Kim, Boyoung et al. (2013) Bifunctional coumarin derivatives that inhibit transthyretin amyloidogenesis and serve as fluorescent transthyretin folding sensors. Chem Commun (Camb) 49:9188-9190 |
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