T cell receptor cross-reactivity expanded by dramatic peptide-MHC adaptability

Nature Chemical Biology
Timothy P RileyBrian M Baker

Abstract

T cell receptor cross-reactivity allows a fixed T cell repertoire to respond to a much larger universe of potential antigens. Recent work has emphasized the importance of peptide structural and chemical homology, as opposed to sequence similarity, in T cell receptor cross-reactivity. Surprisingly, though, T cell receptors can also cross-react between ligands with little physiochemical commonalities. Studying the clinically relevant receptor DMF5, we demonstrate that cross-recognition of such divergent antigens can occur through mechanisms that involve heretofore unanticipated rearrangements in the peptide and presenting MHC protein, including binding-induced peptide register shifts and extensions from MHC peptide binding grooves. Moreover, cross-reactivity can proceed even when such dramatic rearrangements do not translate into structural or chemical molecular mimicry. Beyond demonstrating new principles of T cell receptor cross-reactivity, our results have implications for efforts to predict and control T cell specificity and cross-reactivity and highlight challenges associated with predicting T cell reactivities.

References

Aug 1, 1997·Protein Science : a Publication of the Protein Society·C S MorganS L Mayo
Sep 7, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·P SlizD C Wiley
Oct 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Tanja Kortemme, David Baker
Nov 8, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Verena Rubio-GodoyDanila Valmori
Jun 11, 2003·Nature Immunology·Guillaume B E Stewart-JonesE Yvonne Jones
Jan 27, 2005·Journal of Molecular Biology·Rebecca L Davis-HarrisonBrian M Baker
Mar 23, 2006·Annual Review of Immunology·Markus G RudolphIan A Wilson
Oct 24, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Laura A JohnsonSteven A Rosenberg
Apr 3, 2007·Seminars in Immunology·Kai W WucherpfennigEli E Sercarz
Apr 10, 2007·Cell·Leremy A ColfK Christopher Garcia
Jan 24, 2008·BMC Immunology·John SidneyAlessandro Sette
Apr 16, 2008·Annual Review of Biochemistry·Rhiju Das, David Baker
Sep 20, 2008·The Biochemical Journal·Kathryn M ArmstrongBrian M Baker
Oct 23, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lindsay L JonesDavid M Kranz
Jul 17, 2009·The Journal of Biological Chemistry·David K ColeAndrew K Sewell
Jan 13, 2010·Immunity·Whitney A MacdonaldJames McCluskey
Nov 5, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shalyn C CluteLiisa K Selin
Feb 2, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Oleg Y BorbulevychBrian M Baker
Jan 1, 2009·Methods in Enzymology·Kurt H PiepenbrinkBrian M Baker
Jul 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Oleg Y BorbulevychBrian M Baker
Aug 2, 2011·Nature Immunology·Daniel G PellicciJamie Rossjohn
Nov 22, 2011·The Journal of Biological Chemistry·Linda WooldridgeAndrew K Sewell
Aug 25, 2012·Nature Reviews. Immunology·Andrew K Sewell
Mar 19, 2014·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Thinle ChodonAntoni Ribas
May 27, 2014·Cell·Michael E BirnbaumK Christopher Garcia
Dec 11, 2014·Annual Review of Immunology·Jamie RossjohnJames McCluskey
Jan 15, 2015·Immunology and Cell Biology·John J MilesStephanie Gras
Jan 30, 2016·ELife·Curtis McMurtreyWilliam Hildebrand
Feb 18, 2016·Proceedings of the National Academy of Sciences of the United States of America·Sydney J BlevinsBrian M Baker
Feb 26, 2016·Journal of Immunological Methods·Lance M HellmanBrian M Baker
Apr 21, 2016·Methods in Molecular Biology·Timothy P RileyBrian M Baker
May 18, 2016·The Journal of Clinical Investigation·David K ColeAndrew K Sewell

❮ Previous
Next ❯

Citations

Dec 14, 2018·Proceedings of the National Academy of Sciences of the United States of America·Guo LuoEmmanuel Jean-Marie Mignot
Feb 28, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Charlotte H ColesStephen Harper
Mar 15, 2020·Cells·Inge M N WortelJohannes Textor
Sep 2, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lisa M AssmusNicole L La Gruta
Dec 6, 2019·MedChemComm·Sara LincianoAlessandro Angelini
Sep 19, 2018·Nature Chemical Biology·Stephanie Gras
Aug 19, 2020·Nature Chemical Biology·Jason R DevlinBrian M Baker
Mar 19, 2020·Frontiers in Immunology·Thomas WhalleyBarbara Szomolay
Aug 29, 2020·BMC Medical Genomics·Yi ShiZe-Guang Han
Feb 2, 2021·IScience·Christopher SzetoStephanie Gras
Oct 21, 2020·Thyroid : Official Journal of the American Thyroid Association·Meng ZhangYue Wang
Dec 31, 2020·International Journal of Molecular Sciences·Christopher SzetoStephanie Gras
Nov 17, 2020·Frontiers in Immunology·Chloe H LeeHashem Koohy
Jul 24, 2021·The Journal of Investigative Dermatology·Jörg Christoph Prinz
Jul 30, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stephen ManPierre J Rizkallah
Dec 24, 2021·The Biochemical Journal·Camila R R BarbosaMichele Mishto

❮ Previous
Next ❯

Methods Mentioned

BETA
surface plasmon resonance
size-exclusion chromatography
chips
chip
equilibrium binding
PMA
ELISA
PISA

Software Mentioned

BiaEvaluation
SPR
PyRosetta
Contpro
rigimol
MATLAB
PISA
PyMOL
PHENIX
Discovery Studio

Related Concepts

Related Feeds

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.