Structural basis for self-discrimination by neoantigen-specific TCRs

Finnigan, John P.; Newman, Jenna H.; Patskovsky, Yury; Patskovska, Larysa; Ishizuka, Andrew S.; Lynn, Geoffrey M.; Seder, Robert A.; Krogsgaard, Michelle; Bhardwaj, Nina

doi:10.1038/s41467-024-46367-9

Title: Structural basis for self-discrimination by neoantigen-specific TCRs

Journal Article · 08 March 2024 · Nature Communications

DOI: https://doi.org/10.1038/s41467-024-46367-9 · OSTI ID:2470080

Finnigan, John P. ^[1]; Newman, Jenna H. ^[2]; Patskovsky, Yury ^[3]; Patskovska, Larysa ^[3]; Ishizuka, Andrew S. ^[4]; Lynn, Geoffrey M. ^[4];

^[5];

^[3];

^[6]

Icahn School of Medicine at Mount Sinai, New York, NY (United States); Mount Sinai Hospital, New York, NY (United States); Brigham and Women's Hospital (Harvard Medical School), Boston, MA (United States)
Icahn School of Medicine at Mount Sinai, New York, NY (United States); Mount Sinai Hospital, New York, NY (United States)
New York Univ. (NYU) Grossman School of Medicine, NY (United States); NYU Langone Health, New York, NY (United States)
National Institutes of Health (NIH), Bethesda, MD (United States); Barinthus Biotherapeutics, Germantown, MD (United States)
National Institutes of Health (NIH), Bethesda, MD (United States)
Icahn School of Medicine at Mount Sinai, New York, NY (United States); Mount Sinai Hospital, New York, NY (United States); Parker Inst. for Cancer Immunotherapy, Francisco, CA (United States)

T cell receptors (TCR) are pivotal in mediating tumour cell cytolysis via recognition of mutation-derived tumour neoantigens (neoAgs) presented by major histocompatibility class-I (MHC-I). Understanding the factors governing the emergence of neoAg from somatic mutations is a major focus of current research. However, the structural and cellular determinants controlling TCR recognition of neoAgs remain poorly understood. This study describes the multi-level analysis of a model neoAg from the B16F10 murine melanoma, H2-D^b/Hsf2 p.K72N_68-76, as well as its cognate TCR 47BE7. Through cellular, molecular and structural studies we demonstrate that the p.K72N mutation enhances H2-D^b binding, thereby improving cell surface presentation and stabilizing the TCR 47BE7 epitope. Furthermore, TCR 47BE7 exhibited high functional avidity and selectivity, attributable to a broad, stringent, binding interface enabling recognition of native B16F10 despite low antigen density. Our findings provide insight into the generation of anchor-residue modified neoAg, and emphasize the value of molecular and structural investigations of neoAg in diverse MHC-I contexts for advancing the understanding of neoAg immunogenicity.

View Accepted Manuscript (DOE)

Cite

Export

Save

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2470080

Journal Information:: Nature Communications, Journal Name: Nature Communications Journal Issue: 1 Vol. 15; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

References (82)

Transient Transfection Methods for Preparation of High‐Titer Retroviral Supernatants Pear, Warren Current Protocols in Molecular Biology, Vol. 68, Issue 1 https://doi.org/10.1002/0471142727.mb0911s36	journal	May 2001
Mouse Model for Pre‐Clinical Study of Human Cancer Immunotherapy Ya, Zhiya; Hailemichael, Yared; Overwijk, Willem Current Protocols in Immunology, Vol. 108, Issue 1 https://doi.org/10.1002/0471142735.im2001s108	journal	February 2015
B16 as a Mouse Model for Human Melanoma Overwijk, Willem W.; Restifo, Nicholas P. Current Protocols in Immunology, Vol. 39, Issue 1 https://doi.org/10.1002/0471142735.im2001s39	journal	October 2000
Proline substitution independently enhances H-2D^bcomplex stabilization and TCR recognition of melanoma-associated peptides Uchtenhagen, Hannes; Abualrous, Esam T.; Stahl, Evi European Journal of Immunology, Vol. 43, Issue 11 https://doi.org/10.1002/eji.201343456	journal	August 2013
The three-dimensional structure of H-2Db at 2.4 Å resolution: Implications for antigen-determinant selection Young, Aideen C. M.; Zhang, Weiguo; Sacchettini, James C. Cell, Vol. 76, Issue 1 https://doi.org/10.1016/0092-8674(94)90171-6	journal	January 1994
A Functional Hot Spot for Antigen Recognition in a Superagonist TCR/MHC Complex Degano, Massimo; Garcia, K. Christopher; Apostolopoulos, Vasso Immunity, Vol. 12, Issue 3 https://doi.org/10.1016/S1074-7613(00)80178-8	journal	March 2000
Evidence that Structural Rearrangements and/or Flexibility during TCR Binding Can Contribute to T Cell Activation Krogsgaard, Michelle; Prado, Nelida; Adams, Erin J. Molecular Cell, Vol. 12, Issue 6 https://doi.org/10.1016/S1097-2765(03)00474-X	journal	December 2003
Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study Marabelle, Aurélien; Fakih, Marwan; Lopez, Juanita The Lancet Oncology, Vol. 21, Issue 10 https://doi.org/10.1016/S1470-2045(20)30445-9	journal	October 2020
A Phase Ib Trial of Personalized Neoantigen Therapy Plus Anti-PD-1 in Patients with Advanced Melanoma, Non-small Cell Lung Cancer, or Bladder Cancer Ott, Patrick A.; Hu-Lieskovan, Siwen; Chmielowski, Bartosz Cell, Vol. 183, Issue 2 https://doi.org/10.1016/j.cell.2020.08.053	journal	October 2020
Cytometry by Time-of-Flight Shows Combinatorial Cytokine Expression and Virus-Specific Cell Niches within a Continuum of CD8+ T Cell Phenotypes Newell, Evan W.; Sigal, Natalia; Bendall, Sean C. Immunity, Vol. 36, Issue 1 https://doi.org/10.1016/j.immuni.2012.01.002	journal	January 2012
Oncology Meets Immunology: The Cancer-Immunity Cycle Chen, Daniel S.; Mellman, Ira Immunity, Vol. 39, Issue 1 https://doi.org/10.1016/j.immuni.2013.07.012	journal	July 2013
Resident memory CD8+ T cells in regional lymph nodes mediate immunity to metastatic melanoma Molodtsov, Aleksey K.; Khatwani, Nikhil; Vella, Jennifer L. Immunity, Vol. 54, Issue 9 https://doi.org/10.1016/j.immuni.2021.08.019	journal	September 2021
Development of optimal bicistronic lentiviral vectors facilitates high-level TCR gene expression and robust tumor cell recognition Yang, S.; Cohen, C. J.; Peng, P. D. Gene Therapy, Vol. 15, Issue 21 https://doi.org/10.1038/gt.2008.90	journal	May 2008
Cancer exome analysis reveals a T-cell-dependent mechanism of cancer immunoediting Matsushita, Hirokazu; Vesely, Matthew D.; Koboldt, Daniel C. Nature, Vol. 482, Issue 7385 https://doi.org/10.1038/nature10755	journal	February 2012
Checkpoint blockade cancer immunotherapy targets tumour-specific mutant antigens Gubin, Matthew M.; Zhang, Xiuli; Schuster, Heiko Nature, Vol. 515, Issue 7528 https://doi.org/10.1038/nature13988	journal	November 2014
Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing Yadav, Mahesh; Jhunjhunwala, Suchit; Phung, Qui T. Nature, Vol. 515, Issue 7528 https://doi.org/10.1038/nature14001	journal	November 2014
An immunogenic personal neoantigen vaccine for patients with melanoma Ott, Patrick A.; Hu, Zhuting; Keskin, Derin B. Nature, Vol. 547, Issue 7662 https://doi.org/10.1038/nature22991	journal	July 2017
Personalized RNA mutanome vaccines mobilize poly-specific therapeutic immunity against cancer Sahin, Ugur; Derhovanessian, Evelyna; Miller, Matthias Nature, Vol. 547, Issue 7662 https://doi.org/10.1038/nature23003	journal	July 2017
In vivo CRISPR screening identifies Ptpn2 as a cancer immunotherapy target Manguso, Robert T.; Pope, Hans W.; Zimmer, Margaret D. Nature, Vol. 547, Issue 7664 https://doi.org/10.1038/nature23270	journal	July 2017
Acute emergence and reversion of influenza A virus quasispecies within CD8+ T cell antigenic peptides Valkenburg, Sophie A.; Quiñones-Parra, Sergio; Gras, Stephanie Nature Communications, Vol. 4, Issue 1 https://doi.org/10.1038/ncomms3663	journal	October 2013
T cell killing does not require the formation of a stable mature immunological synapse Purbhoo, Marco A.; Irvine, Darrell J.; Huppa, Johannes B. Nature Immunology, Vol. 5, Issue 5 https://doi.org/10.1038/ni1058	journal	March 2004
Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major Darrah, Patricia A.; Patel, Dipti T.; De Luca, Paula M. Nature Medicine, Vol. 13, Issue 7 https://doi.org/10.1038/nm1592	journal	June 2007
Structural basis for oligoclonal T cell recognition of a shared p53 cancer neoantigen Wu, Daichao; Gallagher, D. Travis; Gowthaman, Ragul Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-16755-y	journal	June 2020
Neoantigen-specific CD8 T cells with high structural avidity preferentially reside in and eliminate tumors Schmidt, Julien; Chiffelle, Johanna; Perez, Marta A. S. Nature Communications, Vol. 14, Issue 1 https://doi.org/10.1038/s41467-023-38946-z	journal	June 2023
Molecular mechanism of phosphopeptide neoantigen immunogenicity Patskovsky, Yury; Natarajan, Aswin; Patskovska, Larysa Nature Communications, Vol. 14, Issue 1 https://doi.org/10.1038/s41467-023-39425-1	journal	June 2023
KRAS G12V neoantigen specific T cell receptor for adoptive T cell therapy against tumors Lu, Dan; Chen, Yuan; Jiang, Min Nature Communications, Vol. 14, Issue 1 https://doi.org/10.1038/s41467-023-42010-1	journal	October 2023
MHC-II neoantigens shape tumour immunity and response to immunotherapy Alspach, Elise; Lussier, Danielle M.; Miceli, Alexander P. Nature, Vol. 574, Issue 7780 https://doi.org/10.1038/s41586-019-1671-8	journal	October 2019
Personalized RNA neoantigen vaccines stimulate T cells in pancreatic cancer Rojas, Luis A.; Sethna, Zachary; Soares, Kevin C. Nature, Vol. 618, Issue 7963 https://doi.org/10.1038/s41586-023-06063-y	journal	May 2023
Peptide–TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens Lynn, Geoffrey M.; Sedlik, Christine; Baharom, Faezzah Nature Biotechnology, Vol. 38, Issue 3 https://doi.org/10.1038/s41587-019-0390-x	journal	January 2020
Structural dissimilarity from self drives neoepitope escape from immune tolerance Devlin, Jason R.; Alonso, Jesus A.; Ayres, Cory M. Nature Chemical Biology, Vol. 16, Issue 11 https://doi.org/10.1038/s41589-020-0610-1	journal	August 2020
Intravenous nanoparticle vaccination generates stem-like TCF1+ neoantigen-specific CD8+ T cells Baharom, Faezzah; Ramirez-Valdez, Ramiro A.; Tobin, Kennedy K. S. Nature Immunology, Vol. 22, Issue 1 https://doi.org/10.1038/s41590-020-00810-3	journal	November 2020
Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer Zacharakis, Nikolaos; Chinnasamy, Harshini; Black, Mary Nature Medicine, Vol. 24, Issue 6 https://doi.org/10.1038/s41591-018-0040-8	journal	June 2018
Immunogenicity and therapeutic targeting of a public neoantigen derived from mutated PIK3CA Chandran, Smita S.; Ma, Jiaqi; Klatt, Martin G. Nature Medicine, Vol. 28, Issue 5 https://doi.org/10.1038/s41591-022-01786-3	journal	April 2022
Low neoantigen expression and poor T-cell priming underlie early immune escape in colorectal cancer Westcott, Peter M. K.; Sacks, Nathan J.; Schenkel, Jason M. Nature Cancer, Vol. 2, Issue 10 https://doi.org/10.1038/s43018-021-00247-z	journal	September 2021
A tissue-based draft map of the murine MHC class I immunopeptidome Schuster, Heiko; Shao, Wenguang; Weiss, Tobias Scientific Data, Vol. 5, Issue 1 https://doi.org/10.1038/sdata.2018.157	journal	August 2018
Plat-E: an efficient and stable system for transient packaging of retroviruses Morita, S.; Kojima, T.; Kitamura, T. Gene Therapy, Vol. 7, Issue 12 https://doi.org/10.1038/sj.gt.3301206	journal	June 2000
Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma Snyder, Alexandra; Makarov, Vladimir; Merghoub, Taha New England Journal of Medicine, Vol. 371, Issue 23 https://doi.org/10.1056/NEJMoa1406498	journal	December 2014
T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer Tran, Eric; Robbins, Paul F.; Lu, Yong-Chen New England Journal of Medicine, Vol. 375, Issue 23 https://doi.org/10.1056/NEJMoa1609279	journal	December 2016
Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden Hellmann, Matthew D.; Ciuleanu, Tudor-Eliade; Pluzanski, Adam New England Journal of Medicine, Vol. 378, Issue 22 https://doi.org/10.1056/NEJMoa1801946	journal	May 2018
Neoantigen T-Cell Receptor Gene Therapy in Pancreatic Cancer Leidner, Rom; Sanjuan Silva, Nelson; Huang, Huayu New England Journal of Medicine, Vol. 386, Issue 22 https://doi.org/10.1056/NEJMoa2119662	journal	June 2022
Effective tumor treatment targeting a melanoma/melanocyte-associated antigen triggers severe ocular autoimmunity Palmer, D. C.; Chan, C. -C.; Gattinoni, L. Proceedings of the National Academy of Sciences, Vol. 105, Issue 23 https://doi.org/10.1073/pnas.0710929105	journal	June 2008
T-cell receptor affinity and avidity defines antitumor response and autoimmunity in T-cell immunotherapy Zhong, S.; Malecek, K.; Johnson, L. A. Proceedings of the National Academy of Sciences, Vol. 110, Issue 17 https://doi.org/10.1073/pnas.1221609110	journal	April 2013
High-affinity oligoclonal TCRs define effective adoptive T cell therapy targeting mutant KRAS-G12D Sim, Malcolm J. W.; Lu, Jinghua; Spencer, Matthew Proceedings of the National Academy of Sciences, Vol. 117, Issue 23 https://doi.org/10.1073/pnas.1921964117	journal	May 2020
Structurally silent peptide anchor modifications allosterically modulate T cell recognition in a receptor-dependent manner Smith, Angela R.; Alonso, Jesus A.; Ayres, Cory M. Proceedings of the National Academy of Sciences, Vol. 118, Issue 4 https://doi.org/10.1073/pnas.2018125118	journal	January 2021
Structural and physical features that distinguish tumor-controlling from inactive cancer neoepitopes Custodio, Jean M.; Ayres, Cory M.; Rosales, Tatiana J. Proceedings of the National Academy of Sciences, Vol. 120, Issue 51 https://doi.org/10.1073/pnas.2312057120	journal	December 2023
HLA-A2-peptide complexes: refolding and crystallization of molecules expressed in Escherichia coli and complexed with single antigenic peptides. Garboczi, D. N.; Hung, D. T.; Wiley, D. C. Proceedings of the National Academy of Sciences, Vol. 89, Issue 8 https://doi.org/10.1073/pnas.89.8.3429	journal	April 1992
Structural Evidence of T Cell Xeno-reactivity in the Absence of Molecular Mimicry Zhao, Rui; Loftus, Douglas J.; Appella, Ettore Journal of Experimental Medicine, Vol. 189, Issue 2 https://doi.org/10.1084/jem.189.2.359	journal	January 1999
Cd8− T Cell Transfectants That Express a High Affinity T Cell Receptor Exhibit Enhanced Peptide-Dependent Activation Holler, Phillip D.; Lim, Alice R.; Cho, Bryan K. The Journal of Experimental Medicine, Vol. 194, Issue 8 https://doi.org/10.1084/jem.194.8.1043	journal	October 2001
Optimized RNP transfection for highly efficient CRISPR/Cas9-mediated gene knockout in primary T cells Seki, Akiko; Rutz, Sascha Journal of Experimental Medicine, Vol. 215, Issue 3 https://doi.org/10.1084/jem.20171626	journal	February 2018
Mutation position is an important determinant for predicting cancer neoantigens Capietto, Aude-Hélène; Jhunjhunwala, Suchit; Pollock, Samuel B. Journal of Experimental Medicine, Vol. 217, Issue 4 https://doi.org/10.1084/jem.20190179	journal	January 2020
Fast and accurate short read alignment with Burrows-Wheeler transform Li, H.; Durbin, R. Bioinformatics, Vol. 25, Issue 14 https://doi.org/10.1093/bioinformatics/btp324	journal	May 2009
TCR3d: The T cell receptor structural repertoire database Gowthaman, Ragul; Pierce, Brian G. Bioinformatics, Vol. 35, Issue 24 https://doi.org/10.1093/bioinformatics/btz517	journal	June 2019
The MHC Motif Atlas: a database of MHC binding specificities and ligands Tadros, Daniel M.; Eggenschwiler, Simon; Racle, Julien Nucleic Acids Research, Vol. 51, Issue D1 https://doi.org/10.1093/nar/gkac965	journal	November 2022
ScanProsite: detection of PROSITE signature matches and ProRule-associated functional and structural residues in proteins de Castro, E.; Sigrist, C. J. A.; Gattiker, A. Nucleic Acids Research, Vol. 34, Issue Web Server https://doi.org/10.1093/nar/gkl124	journal	July 2006
Rosetta FlexPepDock web server—high resolution modeling of peptide–protein interactions London, Nir; Raveh, Barak; Cohen, Eyal Nucleic Acids Research, Vol. 39, Issue suppl_2 https://doi.org/10.1093/nar/gkr431	journal	May 2011
Stable, soluble T-cell receptor molecules for crystallization and therapeutics Boulter, J. M.; Glick, M.; Todorov, P. T. Protein Engineering Design and Selection, Vol. 16, Issue 9 https://doi.org/10.1093/protein/gzg087	journal	September 2003
The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data McKenna, A.; Hanna, M.; Banks, E. Genome Research, Vol. 20, Issue 9 https://doi.org/10.1101/gr.107524.110	journal	July 2010
Low-resolution refinement in the program REFMAC Murshudov, G. N. Acta Crystallographica Section A Foundations of Crystallography, Vol. 67, Issue a1 https://doi.org/10.1107/S0108767311096711	journal	August 2011
Features and development of Coot Emsley, P.; Lohkamp, B.; Scott, W. G. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 4 https://doi.org/10.1107/S0907444910007493	journal	March 2010
A minimal peptide substrate in biotin holoenzyme synthetase-catalyzed biotinylation Beckett, Dorothy; Kovaleva, Elena; Schatz, Peter J. Protein Science, Vol. 8, Issue 4 https://doi.org/10.1110/ps.8.4.921	journal	January 1999
Cancer Regression in Patients After Transfer of Genetically Engineered Lymphocytes Morgan, R. A.; Dudley, M. E.; Wunderlich, J. R. Science, Vol. 314, Issue 5796 https://doi.org/10.1126/science.1129003	journal	October 2006
Cancer Immunotherapy Based on Mutation-Specific CD4+ T Cells in a Patient with Epithelial Cancer Tran, E.; Turcotte, S.; Gros, A. Science, Vol. 344, Issue 6184 https://doi.org/10.1126/science.1251102	journal	May 2014
Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancer Rizvi, Naiyer A.; Hellmann, Matthew D.; Snyder, Alexandra Science, Vol. 348, Issue 6230 https://doi.org/10.1126/science.aaa1348	journal	March 2015
Neoantigens in cancer immunotherapy Schumacher, Ton N.; Schreiber, Robert D. Science, Vol. 348, Issue 6230 https://doi.org/10.1126/science.aaa4971	journal	April 2015
Targeting of cancer neoantigens with donor-derived T cell receptor repertoires Stronen, E.; Toebes, M.; Kelderman, S. Science, Vol. 352, Issue 6291 https://doi.org/10.1126/science.aaf2288	journal	May 2016
Pan-tumor genomic biomarkers for PD-1 checkpoint blockade–based immunotherapy Cristescu, Razvan; Mogg, Robin; Ayers, Mark Science, Vol. 362, Issue 6411 https://doi.org/10.1126/science.aar3593	journal	October 2018
How tcrs bind Mhcs, Peptides, and Coreceptors Rudolph, Markus G.; Stanfield, Robyn L.; Wilson, Ian A. Annual Review of Immunology, Vol. 24, Issue 1 https://doi.org/10.1146/annurev.immunol.23.021704.115658	journal	April 2006
Enhanced Antitumor Activity of T Cells Engineered to Express T-Cell Receptors with a Second Disulfide Bond Cohen, Cyrille J.; Li, Yong F.; El-Gamil, Mona Cancer Research, Vol. 67, Issue 8 https://doi.org/10.1158/0008-5472.CAN-06-3986	journal	April 2007
Exploiting the Mutanome for Tumor Vaccination Castle, John C.; Kreiter, Sebastian; Diekmann, Jan Cancer Research, Vol. 72, Issue 5 https://doi.org/10.1158/0008-5472.CAN-11-3722	journal	March 2012
BRAF Inhibition Increases Tumor Infiltration by T cells and Enhances the Antitumor Activity of Adoptive Immunotherapy in Mice Liu, Chengwen; Peng, Weiyi; Xu, Chunyu Clinical Cancer Research, Vol. 19, Issue 2 https://doi.org/10.1158/1078-0432.CCR-12-1626	journal	January 2013
Abstract CT001: A personalized cancer vaccine, mRNA-4157, combined with pembrolizumab versus pembrolizumab in patients with resected high-risk melanoma: Efficacy and safety results from the randomized, open-label Phase 2 mRNA-4157-P201/Keynote-942 trial Khattak, Adnan; Carlino, Matteo; Meniawy, Tarek Cancer Research, Vol. 83, Issue 8_Supplement https://doi.org/10.1158/1538-7445.AM2023-CT001	journal	May 2023
Altered Binding of Tumor Antigenic Peptides to MHC Class I Affects CD8+ T Cell–Effector Responses Clancy-Thompson, Eleanor; Devlin, Christine A.; Tyler, Paul M. Cancer Immunology Research, Vol. 6, Issue 12 https://doi.org/10.1158/2326-6066.CIR-18-0348	journal	December 2018
Machine-Learning Prediction of Tumor Antigen Immunogenicity in the Selection of Therapeutic Epitopes Smith, Christof C.; Chai, Shengjie; Washington, Amber R. Cancer Immunology Research, Vol. 7, Issue 10 https://doi.org/10.1158/2326-6066.CIR-19-0155	journal	October 2019
An effective mouse model for adoptive cancer immunotherapy targeting neoantigens Hanada, Ken-ichi; Yu, Zhiya; Chappell, Gabrielle R. JCI Insight, Vol. 4, Issue 10 https://doi.org/10.1172/jci.insight.124405	journal	May 2019
Facilitating matched pairing and expression of TCR chains introduced into human T cells Kuball, Jürgen; Dossett, Michelle L.; Wolfl, Matthias Blood, Vol. 109, Issue 6 https://doi.org/10.1182/blood-2006-05-023069	journal	November 2006
Attenuated T Cell Responses to a High-Potency Ligand In Vivo Corse, Emily; Gottschalk, Rachel A.; Krogsgaard, Michelle PLoS Biology, Vol. 8, Issue 9 https://doi.org/10.1371/journal.pbio.1000481	journal	September 2010
Computational Pipeline for the PGV-001 Neoantigen Vaccine Trial Rubinsteyn, Alex; Kodysh, Julia; Hodes, Isaac Frontiers in Immunology, Vol. 8 https://doi.org/10.3389/fimmu.2017.01807	journal	January 2018
T Cell Recognition of Tumor Neoantigens and Insights Into T Cell Immunotherapy Sim, Malcolm J. W.; Sun, Peter D. Frontiers in Immunology, Vol. 13 https://doi.org/10.3389/fimmu.2022.833017	journal	February 2022
Evidence for a TCR Affinity Threshold Delimiting Maximal CD8 T Cell Function Schmid, Daphné A.; Irving, Melita B.; Posevitz, Vilmos The Journal of Immunology, Vol. 184, Issue 9 https://doi.org/10.4049/jimmunol.1000173	journal	March 2010
Eliciting T Cell Immunity Against Poorly Immunogenic Tumors by Immunization with Dendritic Cell-Tumor Fusion Vaccines Wang, Jianli; Saffold, Scott; Cao, Xuetao The Journal of Immunology, Vol. 161, Issue 10 https://doi.org/10.4049/jimmunol.161.10.5516	journal	November 1998
Relevance of the Tumor Antigen in the Validation of Three Vaccination Strategies for Melanoma Bellone, Matteo; Cantarella, Daniela; Castiglioni, Paola The Journal of Immunology, Vol. 165, Issue 5 https://doi.org/10.4049/jimmunol.165.5.2651	journal	September 2000
How H13 Histocompatibility Peptides Differing by a Single Methyl Group and Lacking Conventional MHC Binding Anchor Motifs Determine Self-Nonself Discrimination Ostrov, David A.; Roden, Matthew M.; Shi, Wuxian The Journal of Immunology, Vol. 168, Issue 1 https://doi.org/10.4049/jimmunol.168.1.283	journal	January 2002

Similar Records

DeepNeo: a webserver for predicting immunogenic neoantigens

Journal Article · 2023 · Nucleic Acids Research · OSTI ID:1970388

Kim, Jeong Yeon; Bang, Hyoeun; Noh, Seung-Jae; +1 more

Structure Based Prediction of Neoantigen Immunogenicity

Journal Article · 2019 · Frontiers in Immunology · OSTI ID:1577151

Riley, Timothy P.; Keller, Grant J.; Smith, Angela R.; +4 more

Unraveling a Hotspot for TCR Recognition on HLA-A2: Evidence Against the Existence of Peptide-independent TCR Binding Determinants

Journal Article · 2010 · J. Mol. Biol. · OSTI ID:1008643

Gagnon, Susan J; Borbulevych, Oleg Y; Davis-Harrison, Rebecca L; +7 more

Related Subjects

60 APPLIED LIFE SCIENCES
Oncology
Structural biology
Tumour immunology

Title: Structural basis for self-discrimination by neoantigen-specific TCRs

Citation Formats

References (82)

Similar Records

Related Subjects