Structural basis of a unique interferon-? signaling axis mediated via the receptor IFNAR1

de Weerd, N., Vivian, J., Nguyen, T., Mangan, N., Gould, J., Braniff, S., Zaker-Tabrizi, L., Fung, K., Forster, S., Beddoe, T., Reid, H., Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522 and Hertzog, P. 2013. Structural basis of a unique interferon-? signaling axis mediated via the receptor IFNAR1. Nature Immunology 14 (9) , pp. 901-907. 10.1038/ni.2667

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Abstract

Human T cell antigen receptors (TCRs) pair in millions of combinations to create complex and unique T cell repertoires for each person. Through the use of tetramers to analyze TCRs reactive to the antigen-presenting molecule CD1b, we detected T cells with highly stereotyped TCR α-chains present among genetically unrelated patients with tuberculosis. The germline-encoded, mycolyl lipid-reactive (GEM) TCRs had an α-chain bearing the variable (V) region TRAV1-2 rearranged to the joining (J) region TRAJ9 with few nontemplated (N)-region additions. Analysis of TCRs by high-throughput sequencing, binding and crystallography showed linkage of TCRα sequence motifs to high-affinity recognition of antigen. Thus, the CD1-reactive TCR repertoire is composed of at least two compartments: high-affinity GEM TCRs, and more-diverse TCRs with low affinity for CD1b-lipid complexes. We found high interdonor conservation of TCRs that probably resulted from selection by a nonpolymorphic antigen-presenting molecule and an immunodominant antigen.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	R Medicine > R Medicine (General) R Medicine > RZ Other systems of medicine
Uncontrolled Keywords:	Animals; Disease Models, Animal; Female; Interferon-beta; Lipopolysaccharides; Mice; Mice, Knockout; Models, Molecular; Multiprotein Complexes; Protein Binding; Protein Conformation; Protein Stability; Receptor, Interferon alpha-beta; Shock, Septic; Signal Transduction
Publisher:	Nature Publishing Group
ISSN:	1529-2908
Date of Acceptance:	19 June 2013
Last Modified:	28 Oct 2022 09:51
URI:	https://orca.cardiff.ac.uk/id/eprint/75928

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