ArticleProceedings of the National Academy of Sciences of the United States of America2016
Class II major histocompatibility complex mutant mice to study the germ-line bias of T-cell antigen receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
9 citing papers in PubMed, 13 citations in OpenAlex.
- The Enigmatic Nature of the TCR-pMHC Interaction: Implications for CAR-T and TCR-T Engineering.International journal of molecular sciences · 2022Review
- Immune Equilibrium Depends on the Interaction Between Recognition and Presentation Landscapes.Frontiers in immunology · 2021Review
- MHC-II alleles shape the CDR3 repertoires of conventional and regulatory naïve CD4Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- MHC Restriction: Where Are We Now?Viral immunology · 2020Article
- Inherent reactivity of unselected TCR repertoires to peptide-MHC molecules.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Germline-Encoded TCR-MHC Contacts Promote TCR V Gene Bias in Umbilical Cord Blood T Cell Repertoire.Frontiers in immunology · 2019Article
- Profiling of the TCRβ repertoire in non-model species using high-throughput sequencing.Scientific reports · 2018Article
- Understanding the drivers of MHC restriction of T cell receptors.Nature reviews. Immunology · 2018Review
- Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The interaction of αβ T-cell antigen receptors (TCRs) with peptides bound to MHC molecules lies at the center of adaptive immunity. Whether TCRs have evolved to react with MHC or, instead, processes in the thymus involving coreceptors and other molecules select MHC-specific TCRs de novo from a random repertoire is a longstanding immunological question. Here, using nuclease-targeted mutagenesis, we address this question in vivo by generating three independent lines of knockin mice with single-amino acid mutations of conserved class II MHC amino acids that often are involved in interactions with the germ-line-encoded portions of TCRs. Although the TCR repertoire generated in these mutants is similar in size and diversity to that in WT mice, the evolutionary bias of TCRs for MHC is suggested by a shift and preferential use of some TCR subfamilies over others in mice expressing the mutant class II MHCs. Furthermore, T cells educated on these mutant MHC molecules are alloreactive to each other and to WT cells, and vice versa, suggesting strong functional differences among these repertoires. Taken together, these results highlight both the flexibility of thymic selection and the evolutionary bias of TCRs for MHC.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.