How an alloreactive T-cell receptor achieves peptide and MHC specificity

Wang, Yuan; Singh, Nishant K.; Spear, Timothy T.; Hellman, Lance M.; Piepenbrink, Kurt H.; McMahan, Rachel H.; Rosen, Hugo R.; Vander Kooi, Craig W.; Nishimura, Michael I.; Baker, Brian M.

doi:10.1073/pnas.1700459114

How an alloreactive T-cell receptor achieves peptide and MHC specificity

Journal Article · Thu Jun 01 00:00:00 EDT 2017 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1700459114· OSTI ID:1437463

Wang, Yuan ^[1]; Singh, Nishant K. ^[1]; Spear, Timothy T. ^[2]; Hellman, Lance M. ^[1]; Piepenbrink, Kurt H. ^[3]; McMahan, Rachel H. ^[4]; Rosen, Hugo R. ^[4]; Vander Kooi, Craig W. ^[5]; Nishimura, Michael I. ^[2]; Baker, Brian M. ^[1]

Univ. of Notre Dame, IN (United States). Dept. of Chemistry and Biochemistry; Univ. of Notre Dame, IN (United States). Harper Cancer Research Institute
Loyola Univ. Chicago, Maywood, IL (United States). Dept. of Surgery and Cardinal Bernardin Cancer Center
Univ. of Nebraska, Lincoln, NE (United States)
Univ. of Colorado, Aurora, CO (United States). School of Medicine, Division of Gastroenterology & Hepatology
Univ. of Kentucky, Lexington, KY (United States)

T-cell receptor (TCR) allorecognition is often presumed to be relatively nonspecific, attributable to either a TCR focus on exposed major histocompatibility complex (MHC) polymorphisms or the degenerate recognition of allopeptides. However, paradoxically, alloreactivity can proceed with high peptide and MHC specificity. Although the underlying mechanisms remain unclear, the existence of highly specific alloreactive TCRs has led to their use as immunotherapeutics that can circumvent central tolerance and limit graft-versus-host disease. Here, we show how an alloreactive TCR achieves peptide and MHC specificity. The HCV1406 TCR was cloned from T cells that expanded when a hepatitis C virus (HCV)-infected HLA-A2^-individual received an HLA-A2⁺liver allograft. HCV1406 was subsequently shown to recognize the HCV nonstructural protein 3 (NS3):1406–1415 epitope with high specificity when presented by HLA-A2. Our research shows that NS3/HLA-A2 recognition by the HCV1406 TCR is critically dependent on features unique to both the allo-MHC and the NS3 epitope. We also find cooperativity between structural mimicry and a crucial peptide “hot spot” and demonstrate its role, along with the MHC, in directing the specificity of allorecognition. Our results help explain the paradox of specificity in alloreactive TCRs and have implications for their use in immunotherapy and related efforts to manipulate TCR recognition, as well as alloreactivity in general.

View Accepted Manuscript (DOE)

Research Organization:: Advanced Photon Source (APS), Argonne National Laboratory (ANL), Argonne, IL (US)

Sponsoring Organization:: National Institutes of Health (NIH)

OSTI ID:: 1437463

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 24 Vol. 114; ISSN 0027-8424

Publisher:: National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (67)

Identification of a hepatitis C virus–reactive T cell receptor that does not require CD8 for target cell recognition Callender, Glenda G.; Rosen, Hugo R.; Roszkowski, Jeffrey J. Hepatology, Vol. 43, Issue 5 https://doi.org/10.1002/hep.21157	journal	January 2006
T cell receptor bias for MHC: co-evolution or co-receptors? Rangarajan, Sneha; Mariuzza, Roy A. Cellular and Molecular Life Sciences, Vol. 71, Issue 16 https://doi.org/10.1007/s00018-014-1600-9	journal	March 2014
TCR gene-modified T cells can efficiently treat established hepatitis C-associated hepatocellular carcinoma tumors Spear, Timothy T.; Callender, Glenda G.; Roszkowski, Jeffrey J. Cancer Immunology, Immunotherapy, Vol. 65, Issue 3 https://doi.org/10.1007/s00262-016-1800-2	journal	February 2016
Exploring the gas access routes in a [NiFeSe] hydrogenase using crystals pressurized with krypton and oxygen Zacarias, Sónia; Temporão, Adriana; Carpentier, Philippe JBIC Journal of Biological Inorganic Chemistry, Vol. 25, Issue 6 https://doi.org/10.1007/s00775-020-01814-y	journal	August 2020
What Is Direct Allorecognition? Boardman, Dominic A.; Jacob, Jacinta; Smyth, Lesley A. Current Transplantation Reports, Vol. 3, Issue 4 https://doi.org/10.1007/s40472-016-0115-8	journal	October 2016
Why do so many lymphocytes respond to major histocompatibility antigens? Matzinger, Polly; Bevan, Michael J. Cellular Immunology, Vol. 29, Issue 1 https://doi.org/10.1016/0008-8749(77)90269-6	journal	March 1977
High determinant density may explain the phenomenon of alloreactivity Bevan, Michael J. Immunology Today, Vol. 5, Issue 5 https://doi.org/10.1016/0167-5699(84)90233-0	journal	May 1984
WHAT IF: A molecular modeling and drug design program Vriend, G. Journal of Molecular Graphics, Vol. 8, Issue 1 https://doi.org/10.1016/0263-7855(90)80070-V	journal	March 1990
A Structural Basis for the Selection of Dominant αβ T Cell Receptors in Antiviral Immunity Kjer-Nielsen, Lars; Clements, Craig S.; Purcell, Anthony W. Immunity, Vol. 18, Issue 1 https://doi.org/10.1016/S1074-7613(02)00513-7	journal	January 2003
How a Single T Cell Receptor Recognizes Both Self and Foreign MHC Colf, Leremy A.; Bankovich, Alexander J.; Hanick, Nicole A. Cell, Vol. 129, Issue 1 https://doi.org/10.1016/j.cell.2007.01.048	journal	April 2007
Deconstructing the Peptide-MHC Specificity of T Cell Recognition Birnbaum, Michael E.; Mendoza, Juan L.; Sethi, Dhruv K. Cell, Vol. 157, Issue 5 https://doi.org/10.1016/j.cell.2014.03.047	journal	May 2014
T-cells behaving badly: structural insights into alloreactivity and autoimmunity Ely, Lauren K.; Burrows, Scott R.; Purcell, Anthony W. Current Opinion in Immunology, Vol. 20, Issue 5 https://doi.org/10.1016/j.coi.2008.07.006	journal	October 2008
T Cell Allorecognition via Molecular Mimicry Macdonald, Whitney A.; Chen, Zhenjun; Gras, Stephanie Immunity, Vol. 31, Issue 6 https://doi.org/10.1016/j.immuni.2009.09.025	journal	December 2009
T Cell Receptor Signaling Is Limited by Docking Geometry to Peptide-Major Histocompatibility Complex Adams, Jarrett J.; Narayanan, Samanthi; Liu, Baoyu Immunity, Vol. 35, Issue 5 https://doi.org/10.1016/j.immuni.2011.09.013	journal	November 2011
Reversed T Cell Receptor Docking on a Major Histocompatibility Class I Complex Limits Involvement in the Immune Response Gras, Stephanie; Chadderton, Jesseka; Del Campo, Claudia M. Immunity, Vol. 45, Issue 4 https://doi.org/10.1016/j.immuni.2016.09.007	journal	October 2016
T-cell allorecognition: a case of mistaken identity or déjà vu? Archbold, Julia K.; Macdonald, Whitney A.; Burrows, Scott R. Trends in Immunology, Vol. 29, Issue 5 https://doi.org/10.1016/j.it.2008.02.005	journal	May 2008
Reconciling views on T cell receptor germline bias for MHC Garcia, K. Christopher Trends in Immunology, Vol. 33, Issue 9 https://doi.org/10.1016/j.it.2012.05.005	journal	September 2012
MHC restriction is imposed on a diverse T cell receptor repertoire by CD4 and CD8 co-receptors during thymic selection Van Laethem, François; Tikhonova, Anastasia N.; Singer, Alfred Trends in Immunology, Vol. 33, Issue 9 https://doi.org/10.1016/j.it.2012.05.006	journal	September 2012
Differential scanning fluorimetry based assessments of the thermal and kinetic stability of peptide–MHC complexes Hellman, Lance M.; Yin, Liusong; Wang, Yuan Journal of Immunological Methods, Vol. 432 https://doi.org/10.1016/j.jim.2016.02.016	journal	May 2016
Two Different T Cell Receptors use Different Thermodynamic Strategies to Recognize the Same Peptide/MHC Ligand Davis-Harrison, Rebecca L.; Armstrong, Kathryn M.; Baker, Brian M. Journal of Molecular Biology, Vol. 346, Issue 2 https://doi.org/10.1016/j.jmb.2004.11.063	journal	February 2005
Inference of Macromolecular Assemblies from Crystalline State Krissinel, Evgeny; Henrick, Kim Journal of Molecular Biology, Vol. 372, Issue 3 https://doi.org/10.1016/j.jmb.2007.05.022	journal	September 2007
Structures of MART-126/27–35 Peptide/HLA-A2 Complexes Reveal a Remarkable Disconnect between Antigen Structural Homology and T Cell Recognition Borbulevych, Oleg Y.; Insaidoo, Francis K.; Baxter, Tiffany K. Journal of Molecular Biology, Vol. 372, Issue 5 https://doi.org/10.1016/j.jmb.2007.07.025	journal	October 2007
The Phenix software for automated determination of macromolecular structures Adams, Paul D.; Afonine, Pavel V.; Bunkóczi, Gábor Methods, Vol. 55, Issue 1 https://doi.org/10.1016/j.ymeth.2011.07.005	journal	September 2011
The basis for limited specificity and MHC restriction in a T cell receptor interface Piepenbrink, Kurt H.; Blevins, Sydney J.; Scott, Daniel R. Nature Communications, Vol. 4, Issue 1 https://doi.org/10.1038/ncomms2948	journal	June 2013
Genetic variation in MHC proteins is associated with T cell receptor expression biases Sharon, Eilon; Sibener, Leah V.; Battle, Alexis Nature Genetics, Vol. 48, Issue 9 https://doi.org/10.1038/ng.3625	journal	August 2016
T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex Beringer, Dennis X.; Kleijwegt, Fleur S.; Wiede, Florian Nature Immunology, Vol. 16, Issue 11 https://doi.org/10.1038/ni.3271	journal	October 2015
Structural interplay between germline interactions and adaptive recognition determines the bandwidth of TCR-peptide-MHC cross-reactivity Adams, Jarrett J.; Narayanan, Samanthi; Birnbaum, Michael E. Nature Immunology, Vol. 17, Issue 1 https://doi.org/10.1038/ni.3310	journal	November 2015
CDR3 loop flexibility contributes to the degeneracy of TCR recognition Reiser, Jean-Baptiste; Darnault, Claudine; Grégoire, Claude Nature Immunology, Vol. 4, Issue 3 https://doi.org/10.1038/ni891	journal	February 2003
Specificity of T-cell alloreactivity Felix, Nathan J.; Allen, Paul M. Nature Reviews Immunology, Vol. 7, Issue 12 https://doi.org/10.1038/nri2200	journal	December 2007
Structural and energetic evidence for highly peptide-specific tumor antigen targeting via allo-MHC restriction Simpson, A. A.; Mohammed, F.; Salim, M. Proceedings of the National Academy of Sciences, Vol. 108, Issue 52 https://doi.org/10.1073/pnas.1108422109	journal	December 2011
Alloreactive cytotoxic T cells provide means to decipher the immunopeptidome and reveal a plethora of tumor-associated self-epitopes Kumari, S.; Walchli, S.; Fallang, L. -E. Proceedings of the National Academy of Sciences, Vol. 111, Issue 1 https://doi.org/10.1073/pnas.1306549111	journal	December 2013
How structural adaptability exists alongside HLA-A2 bias in the human αβ TCR repertoire Blevins, Sydney J.; Pierce, Brian G.; Singh, Nishant K. Proceedings of the National Academy of Sciences, Vol. 113, Issue 9 https://doi.org/10.1073/pnas.1522069113	journal	February 2016
Peptide-specific cytotoxic T lymphocytes restricted by nonself major histocompatibility complex class I molecules: Reagents for tumor immunotherapy Sadovnikova, E.; Stauss, H. J. Proceedings of the National Academy of Sciences, Vol. 93, Issue 23 https://doi.org/10.1073/pnas.93.23.13114	journal	November 1996
Different T Cell Receptor Affinity Thresholds and CD8 Coreceptor Dependence Govern Cytotoxic T Lymphocyte Activation and Tetramer Binding Properties Laugel, Bruno; van den Berg, Hugo A.; Gostick, Emma Journal of Biological Chemistry, Vol. 282, Issue 33 https://doi.org/10.1074/jbc.M700976200	journal	May 2007
Peptide-independent Recognition by Alloreactive Cytotoxic T Lymphocytes (CTL) Smith, Pamela A.; Brunmark, Anders; Jackson, Michael R. The Journal of Experimental Medicine, Vol. 185, Issue 6 https://doi.org/10.1084/jem.185.6.1023	journal	March 1997
Structure of a Complex of the Human α/β T Cell Receptor (TCR) HA1.7, Influenza Hemagglutinin Peptide, and Major Histocompatibility Complex Class II Molecule, HLA-DR4 (DRA0101 and DRB10401): Insight into TCR Cross-Restriction and Alloreactivity Hennecke, Jens; Wiley, Don C. The Journal of Experimental Medicine, Vol. 195, Issue 5 https://doi.org/10.1084/jem.20011194	journal	February 2002
A Naturally Selected Dimorphism within the HLA-B44 Supertype Alters Class I Structure, Peptide Repertoire, and T Cell Recognition Macdonald, Whitney A.; Purcell, Anthony W.; Mifsud, Nicole A. The Journal of Experimental Medicine, Vol. 198, Issue 5 https://doi.org/10.1084/jem.20030066	journal	August 2003
Dual, HLA-B27 Subtype-dependent Conformation of a Self-peptide Hülsmeyer, Martin; Fiorillo, Maria Teresa; Bettosini, Francesca The Journal of Experimental Medicine, Vol. 199, Issue 2 https://doi.org/10.1084/jem.20031690	journal	January 2004
Gapped sequence alignment using artificial neural networks: application to the MHC class I system Andreatta, Massimo; Nielsen, Morten Bioinformatics, Vol. 32, Issue 4 https://doi.org/10.1093/bioinformatics/btv639	journal	October 2015
NetMHC-3.0: accurate web accessible predictions of human, mouse and monkey MHC class I affinities for peptides of length 8–11 Lundegaard, Claus; Lamberth, Kasper; Harndahl, Mikkel Nucleic Acids Research, Vol. 36, Issue suppl_2 https://doi.org/10.1093/nar/gkn202	journal	May 2008
The IMGT/HLA database Robinson, J.; Mistry, K.; McWilliam, H. Nucleic Acids Research, Vol. 39, Issue Database https://doi.org/10.1093/nar/gkq998	journal	November 2010
The IMGT/HLA database Robinson, James; Halliwell, Jason A.; McWilliam, Hamish Nucleic Acids Research, Vol. 41, Issue D1 https://doi.org/10.1093/nar/gks949	journal	October 2012
Phaser crystallographic software McCoy, Airlie J.; Grosse-Kunstleve, Ralf W.; Adams, Paul D. Journal of Applied Crystallography, Vol. 40, Issue 4 https://doi.org/10.1107/S0021889807021206	journal	July 2007
Use of TLS parameters to model anisotropic displacements in macromolecular refinement Winn, M. D.; Isupov, M. N.; Murshudov, G. N. Acta Crystallographica Section D Biological Crystallography, Vol. 57, Issue 1 https://doi.org/10.1107/S0907444900014736	journal	January 2001
MolProbity : all-atom structure validation for macromolecular crystallography Chen, Vincent B.; Arendall, W. Bryan; Headd, Jeffrey J. Acta Crystallographica Section D Biological Crystallography, Vol. 66, Issue 1 https://doi.org/10.1107/S0907444909042073	journal	December 2009
Reliable prediction of T-cell epitopes using neural networks with novel sequence representations Nielsen, Morten; Lundegaard, Claus; Worning, Peder Protein Science, Vol. 12, Issue 5 https://doi.org/10.1110/ps.0239403	journal	May 2003
Structural Basis of Plasticity in T Cell Receptor Recognition of a Self Peptide-MHC Antigen Garcia, K. C. Science, Vol. 279, Issue 5354 https://doi.org/10.1126/science.279.5354.1166	journal	February 1998
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
Evolutionarily Conserved Amino Acids That Control TCR-MHC Interaction Marrack, Philippa; Scott-Browne, James P.; Dai, Shaodong Annual Review of Immunology, Vol. 26, Issue 1 https://doi.org/10.1146/annurev.immunol.26.021607.090421	journal	April 2008
Influence of Human CD8 on Antigen Recognition by T-Cell Receptor-Transduced Cells Lyons, G. E.; Moore, T.; Brasic, N. Cancer Research, Vol. 66, Issue 23 https://doi.org/10.1158/0008-5472.CAN-06-2379	journal	November 2006
Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity Cole, David K.; Bulek, Anna M.; Dolton, Garry Journal of Clinical Investigation, Vol. 126, Issue 6 https://doi.org/10.1172/JCI85679	journal	May 2016
Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity Cole, David K.; Bulek, Anna M.; Dolton, Garry Journal of Clinical Investigation, Vol. 126, Issue 9 https://doi.org/10.1172/jci89919	journal	August 2016
Successful treatment of EBV-associated posttransplantation lymphoma after cord blood transplantation using third-party EBV-specific cytotoxic T lymphocytes Barker, Juliet N.; Doubrovina, Ekaterina; Sauter, Craig Blood, Vol. 116, Issue 23 https://doi.org/10.1182/blood-2010-04-281873	journal	December 2010
Off-the-shelf T-cell therapy Cooper, Laurence J. N. Blood, Vol. 116, Issue 23 https://doi.org/10.1182/blood-2010-10-308379	journal	December 2010
Modeling T cell receptor recognition of CD1-lipid and MR1-metabolite complexes Pierce, Brian G.; Vreven, Thom; Weng, Zhiping BMC Bioinformatics, Vol. 15, Issue 1 https://doi.org/10.1186/1471-2105-15-319	journal	September 2014
Generating quantitative models describing the sequence specificity of biological processes with the stabilized matrix method Peters, Bjoern; Sette, Alessandro BMC Bioinformatics, Vol. 6, Issue 1 https://doi.org/10.1186/1471-2105-6-132	journal	May 2005
HLA class I supertypes: a revised and updated classification Sidney, John; Peters, Bjoern; Frahm, Nicole BMC Immunology, Vol. 9, Issue 1 https://doi.org/10.1186/1471-2172-9-1	journal	January 2008
Quantitative peptide binding motifs for 19 human and mouse MHC class I molecules derived using positional scanning combinatorial peptide libraries Sidney, John; Assarsson, Erika; Moore, Carrie Immunome Research, Vol. 4, Issue 1 https://doi.org/10.1186/1745-7580-4-2	journal	January 2008
Hepatitis C virus-cross-reactive TCR gene-modified T cells: a model for immunotherapy against diseases with genomic instability Spear, Timothy T.; Riley, Timothy P.; Lyons, Gretchen E. Journal of Leukocyte Biology, Vol. 100, Issue 3 https://doi.org/10.1189/jlb.2A1215-561R	journal	February 2016
Modeling T cell receptor recognition of CD1-lipid and MR1-metabolite complexes Pierce, Brian G.; Vreven, Thom; Weng, Zhiping Springer Nature https://doi.org/10.13016/zoyr-hhrh	text	January 2014
Clustering HLA Class I Superfamilies Using Structural Interaction Patterns Harjanto, Sumitro; Ng, Lisa F. P.; Tong, Joo Chuan PLoS ONE, Vol. 9, Issue 1 https://doi.org/10.1371/journal.pone.0086655	journal	January 2014
Conformational Flexibility of the MHC Class I α1-α2 Domain in Peptide Bound and Free States: A Molecular Dynamics Simulation Study Zacharias, Martin; Springer, Sebastian Biophysical Journal, Vol. 87, Issue 4 https://doi.org/10.1529/biophysj.104.044743	journal	October 2004
The Immune Epitope Database and Analysis Resource in Epitope Discovery and Synthetic Vaccine Design Fleri, Ward; Paul, Sinu; Dhanda, Sandeep Kumar Frontiers in Immunology, Vol. 8 https://doi.org/10.3389/fimmu.2017.00278	journal	March 2017
TCRs Used in Cancer Gene Therapy Cross-React with MART-1/Melan-A Tumor Antigens via Distinct Mechanisms Borbulevych, Oleg Y.; Santhanagopolan, Sujatha M.; Hossain, Moushumi The Journal of Immunology, Vol. 187, Issue 5 https://doi.org/10.4049/jimmunol.1101268	journal	July 2011
Quantifying the Frequency of Alloreactive T Cells In Vivo: New Answers to an Old Question Suchin, Elliot J.; Langmuir, Peter B.; Palmer, Ed The Journal of Immunology, Vol. 166, Issue 2 https://doi.org/10.4049/jimmunol.166.2.973	journal	January 2001
Crystal Structures of Two Closely Related but Antigenically Distinct HLA-A2/Melanocyte-Melanoma Tumor-Antigen Peptide Complexes Sliz, Piotr; Michielin, Olivier; Cerottini, Jean-Charles The Journal of Immunology, Vol. 167, Issue 6 https://doi.org/10.4049/jimmunol.167.6.3276	journal	September 2001
Cutting Edge: Identification of Hepatitis C Virus-Specific CD8 ⁺ T Cells Restricted by Donor HLA Alleles following Liver Transplantation Rosen, Hugo R.; Hinrichs, David J.; Leistikow, Rachel L. The Journal of Immunology, Vol. 173, Issue 9 https://doi.org/10.4049/jimmunol.173.9.5355	journal	October 2004

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
59 BASIC BIOLOGICAL SCIENCES
T-cell receptor
alloreactivity
peptide-MHC
specificity
structure

How an alloreactive T-cell receptor achieves peptide and MHC specificity

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