T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex

Beringer, Dennis X., Kleijwegt, Fleur S., Wiede, Florian, Van Der Slik, Arno R., Loh, Khai Lee, Petersen, Jan, Dudek, Nadine L., Duinkerken, Gaby, Laban, Sandra, Joosten, Antoinette, Vivian, Julian P., Chen, Zhenjun, Uldrich, Anthony W., Godfrey, Dale I., McCluskey, James, Price, David A., Radford, Kristen J., Purcell, Anthony W., Nikolic, Tatjana, Reid, Hugh H., Tiganis, Tony, Roep, Bart O. and Rossjohn, Jamie (2015) T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex. Nature Immunology, 16 11: 1153-1161. doi:10.1038/ni.3271

Author Beringer, Dennis X.
Kleijwegt, Fleur S.
Wiede, Florian
Van Der Slik, Arno R.
Loh, Khai Lee
Petersen, Jan
Dudek, Nadine L.
Duinkerken, Gaby
Laban, Sandra
Joosten, Antoinette
Vivian, Julian P.
Chen, Zhenjun
Uldrich, Anthony W.
Godfrey, Dale I.
McCluskey, James
Price, David A.
Radford, Kristen J.
Purcell, Anthony W.
Nikolic, Tatjana
Reid, Hugh H.
Tiganis, Tony
Roep, Bart O.
Rossjohn, Jamie
Title T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex
Journal name Nature Immunology   Check publisher's open access policy
ISSN 1529-2916
Publication date 2015-11-01
Year available 2015
Sub-type Article (original research)
DOI 10.1038/ni.3271
Open Access Status Not yet assessed
Volume 16
Issue 11
Start page 1153
End page 1161
Total pages 9
Place of publication New York, United States
Publisher Nature Publishing Group
Collection year 2016
Language eng
Formatted abstract
Central to adaptive immunity is the interaction between the αβ T cell receptor (TCR) and peptide presented by the major histocompatibility complex (MHC) molecule. Presumably reflecting TCR-MHC bias and T cell signaling constraints, the TCR universally adopts a canonical polarity atop the MHC. We report the structures of two TCRs, derived from human induced T regulatory (iTreg) cells, complexed to an MHC class II molecule presenting a proinsulin-derived peptide. The ternary complexes revealed a 180° polarity reversal compared to all other TCR-peptide-MHC complex structures. Namely, the iTreg TCR α-chain and β-chain are overlaid with the α-chain and β-chain of MHC class II, respectively. Nevertheless, this TCR interaction elicited a peptide-reactive, MHC-restricted T cell signal. Thus TCRs are not 'hardwired' to interact with MHC molecules in a stereotypic manner to elicit a T cell signal, a finding that fundamentally challenges our understanding of TCR recognition.
Keyword Antigen processing and presentation
X-ray crystallography
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Mater Research Institute-UQ (MRI-UQ)
Official 2016 Collection
School of Biomedical Sciences Publications
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 17 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 20 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Tue, 10 Nov 2015, 03:48:15 EST by System User on behalf of Scholarly Communication and Digitisation Service