Van Rhijn, I., Kasmar, A., de Jong, A., Gras, S., Bhati, M., Doorenspleet, M., de Vries, N., Godfrey, D., Altman, J., de Jager, W., Rossjohn, Jamie  ORCID: https://orcid.org/0000-0002-2020-7522 and Moody, D.
2013.
A conserved human T cell population targets mycobacterial antigens presented by CD1b.
Nature Immunology
14
(7)
, pp. 706-713.
10.1038/ni.2630
|
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: | Schools > Medicine Research Institutes & Centres > Systems Immunity Research Institute (SIURI) |
| Subjects: | R Medicine > R Medicine (General) R Medicine > RZ Other systems of medicine |
| Uncontrolled Keywords: | Amino Acid Sequence; Antigens, CD1; Base Sequence; Clone Cells; Crystallography, X-Ray; Flow Cytometry; Humans; Models, Molecular; Molecular Sequence Data; Mycobacterium; Mycobacterium Infections; Receptors, Antigen, T-Cell, alpha-beta; Reverse Transcriptase Polymerase Chain Reaction; RNA; Sequence Analysis, DNA; T-Lymphocyte Subsets; T-Lymphocytes |
| Publisher: | Nature Publishing Group |
| ISSN: | 1529-2908 |
| Date of Acceptance: | 29 April 2013 |
| Last Modified: | 28 Oct 2022 09:51 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/75926 |
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