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Comprehensive analysis of structural and sequencing data reveals almost unconstrained chain pairing in TCRαβ complex
- Source :
- PLoS Computational Biology, Vol 16, Iss 3, p e1007714 (2020), PLoS Computational Biology
- Publication Year :
- 2020
- Publisher :
- Public Library of Science (PLoS), 2020.
-
Abstract
- Antigen recognition by T-cells is guided by the T-cell receptor (TCR) heterodimer formed by α and β chains. A huge diversity of TCR sequences should be maintained by the immune system in order to be able to mount an effective response towards foreign pathogens, so, due to cooperative binding of α and β chains to the pathogen, any constraints on chain pairing can have a profound effect on immune repertoire structure, diversity and antigen specificity. By integrating available structural data and paired chain sequencing results we were able to show that there are almost no constraints on pairing in TCRαβ complexes, allowing naive T-cell repertoire to reach the highest possible diversity. Additional analysis reveals that the specific choice of contacting amino acids can still have a profound effect on complex conformation. Moreover, antigen-driven selection can distort the uniform landscape of chain pairing, while small, yet significant, differences in the pairing can be attributed to various specialized T-cell subsets such as MAIT and iNKT T-cells, as well as other TCR sets specific to certain antigens.<br />Author summary In the present paper we study chain pairing preferences in the T-cell receptor (TCR) heterodimer complex. The TCR molecule is formed by α and β chains and binding of both of these chains to an antigen presented by the major histocompatibility complex (MHC) molecule is required in order to trigger an immune response against foreign pathogens and neoantigens. We show that chain pairing in the TCR complex is nearly random ensuring a highly diverse set of TCRs required for recognition of a vast set of antigens. Our results also show that chain pairing preferences can nevertheless influence TCR complex geometry and biases in TCR chain pairing can be used to identify antigen-driven selection or selection towards specialized subsets of T-cells such as mucosal-associated and natural killer invariant T-cells.
- Subjects :
- 0301 basic medicine
Physiology
Protein Conformation
Receptors, Antigen, T-Cell, alpha-beta
Antigen Processing and Recognition
Immune Receptors
Biochemistry
Major Histocompatibility Complex
White Blood Cells
Database and Informatics Methods
Mice
0302 clinical medicine
Chain (algebraic topology)
Animal Cells
Immune Physiology
Medicine and Health Sciences
Amino Acids
Biology (General)
Databases, Protein
chemistry.chemical_classification
Immune System Proteins
Ecology
biology
T Cells
Chemistry
Repertoire
Amino acid
Order (biology)
Computational Theory and Mathematics
Modeling and Simulation
Amino Acid Analysis
Cellular Types
Sequence Analysis
Research Article
Signal Transduction
Bioinformatics
Sequence analysis
QH301-705.5
Immune Cells
Sequencing data
Immunology
Sequence Databases
Computational biology
Research and Analysis Methods
Major histocompatibility complex
03 medical and health sciences
Cellular and Molecular Neuroscience
Antigen
Genetics
Animals
Humans
Antigens
Molecular Biology Techniques
Molecular Biology
Ecology, Evolution, Behavior and Systematics
Molecular Biology Assays and Analysis Techniques
Blood Cells
T-cell receptor
Biology and Life Sciences
Proteins
Computational Biology
Cooperative binding
Cell Biology
T Cell Receptors
Biological Databases
030104 developmental biology
Pairing
biology.protein
Clinical Immunology
Clinical Medicine
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 15537358
- Volume :
- 16
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS Computational Biology
- Accession number :
- edsair.doi.dedup.....67b3df9de469267fbb95f17688b4bd59