This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. alpha-beta T cell receptors (TCRs) recognize peptide antigens bound and presented by major histocompatibility complex (MHC) proteins. Although T cell receptor cross-reactivity is a fundamental property of the immune system and is implicated in the immune response to cancer and numerous autoimmune pathologies, the molecular mechanisms by which TCRs can recognize and respond to diverse ligands are poorly understood. In our NIH and ACS funded work, we are seeking insight into TCR cross-reactivity through investigations of the structural and biophysical properties of TCR-pMHC interactions, and our studies involve structural determination of TCR-peptide/MHC complexes as well as unligated TCRs and peptide/MHC molecules. Structural properties are related to biophysical and immunological data. Recent findings we aim to build on with additional synchrotron time include: 1) observations that TCR recognition can proceed with cooperative structural changes occurring on both sides of the interface (Gagnon et al., J Mol Biol 363 2006 and unpublished crystallographic data) and 2) observations that subtle substitutions in antigenic peptides can have complex structural consequences, the immunological consequences of which are difficult to reconcile with current models of TCR recognition (Borbulevych et al., J Mol Biol 372 2007). The latter observations are of particular interest in the design of altered peptides for use in cancer immunotherapy (e.g., Borbulevych et al. J Immunol 174 2005). Experiments planned for the near future include structural studies of different TCRs bound to the same peptide/MHC complex and studies of peptide/MHC variants designed to elicit improved immunological responses with T cells specific for the tumor antigen Melan-A/MART-1.
| Weingarten, Adam S; Dannenhoffer, Adam J; Kazantsev, Roman V et al. (2018) Chromophore Dipole Directs Morphology and Photocatalytic Hydrogen Generation. J Am Chem Soc 140:4965-4968 |
| Yang, Cheolhee; Choi, Minseo; Kim, Jong Goo et al. (2018) Protein Structural Dynamics of Wild-Type and Mutant Homodimeric Hemoglobin Studied by Time-Resolved X-Ray Solution Scattering. Int J Mol Sci 19: |
| Kazantsev, Roman V; Dannenhoffer, Adam J; Weingarten, Adam S et al. (2017) Crystal-Phase Transitions and Photocatalysis in Supramolecular Scaffolds. J Am Chem Soc 139:6120-6127 |
| Fournier, Bertrand; Sokolow, Jesse; Coppens, Philip (2016) Analysis of multicrystal pump-probe data sets. II. Scaling of ratio data sets. Acta Crystallogr A Found Adv 72:250-60 |
| Cho, Hyun Sun; Schotte, Friedrich; Dashdorj, Naranbaatar et al. (2016) Picosecond Photobiology: Watching a Signaling Protein Function in Real Time via Time-Resolved Small- and Wide-Angle X-ray Scattering. J Am Chem Soc 138:8815-23 |
| Pande, Kanupriya; Hutchison, Christopher D M; Groenhof, Gerrit et al. (2016) Femtosecond structural dynamics drives the trans/cis isomerization in photoactive yellow protein. Science 352:725-9 |
| Weingarten, Adam S; Kazantsev, Roman V; Palmer, Liam C et al. (2015) Supramolecular Packing Controls H? Photocatalysis in Chromophore Amphiphile Hydrogels. J Am Chem Soc 137:15241-6 |
| Pfoh, Roland; Pai, Emil F; Saridakis, Vivian (2015) Nicotinamide mononucleotide adenylyltransferase displays alternate binding modes for nicotinamide nucleotides. Acta Crystallogr D Biol Crystallogr 71:2032-9 |
| Mariette, Céline; Guérin, Laurent; Rabiller, Philippe et al. (2015) The creation of modulated monoclinic aperiodic composites in n-alkane/urea compounds. Z Kristallogr Cryst Mater 230:5-11 |
| Yang, Xiaojing; Stojkovi?, Emina A; Ozarowski, Wesley B et al. (2015) Light Signaling Mechanism of Two Tandem Bacteriophytochromes. Structure 23:1179-89 |
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