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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
1R01AI042266-01
Application #
2453673
Study Section
Allergy and Immunology Study Section (ALY)
Project Start
1998-01-01
Project End
2002-12-31
Budget Start
1998-01-01
Budget End
1998-12-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Gunn, Robin J; Herrin, Brantley R; Acharya, Sharmistha et al. (2018) VLR Recognition of TLR5 Expands the Molecular Characterization of Protein Antigen Binding by Non-Ig-based Antibodies. J Mol Biol 430:1350-1367
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

Showing the most recent 10 out of 68 publications