The somatically generated portion of the T cell receptor CDR3α contributes to the MHC allele specificity of the T cell receptor
- Howard Hughes Medical Institute, National Jewish Health, United States
- University of Colorado School of Medicine, United States
- National Jewish Health, United States
- La Jolla Institute for Allergy and Immunology, United States
Abstract
Mature T cells bearing αβ T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor β chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor α and β chain and, surprisingly, dramatically affected by the non germ line encoded portions of CDR3 of the T cell receptor α chain. Thus, in addition to determining specificity for antigen, the non germline encoded elements of T cell receptors may help the proteins cope with the extremely polymorphic nature of major histocompatibility complex products within the species.
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Funding
National Institutes of Health (AI 18785)
- Philippa Marrack
National Institutes of Health (AI 092108)
- Laurent Gapin
National Institutes of Health (AI 103736)
- Laurent Gapin
Howard Hughes Medical Institute (NA)
- John Kappler
National Institutes of Health (DK099317)
- Maki Nakayama
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (AC-2517) of National Jewish Health. The protocol was approved by the Institutional Animal Care and Use Committee of National Jewish Health. Every effort was made to minimize suffering.
Copyright
© 2017, Marrack et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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The somatically generated portion of the T cell receptor CDR3α contributes to the MHC allele specificity of the T cell receptor
eLife 6:e30918.
https://doi.org/10.7554/eLife.30918
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