Structural basis for enabling T-cell receptor diversity within biased virus-specific CD8+ T-cell responses
E Bridie Day1, Carole Guillonneau, Stephanie Gras
1Department of Microbiology and Immunology, Bio21, Department of Biochemistry, University of Melbourne, Parkville, VIC 3010, Australia.
Summary
T-cell receptor (TCR) V-region bias, driven by specific gene segments like TRBV29, allows for diverse peptide recognition. TCR flexibility in V-region use, particularly CDR3β length, maintains specificity for pathogen-derived peptides.
Area of Science:
- Immunology
- Molecular Biology
- Structural Biology
Background:
- Pathogen-specific immune responses involve T-cell receptors (TCRs) recognizing peptide-MHC class I (pMHCI) complexes.
- The selection of TCR variable (V)-regions and their impact on TCR heterodimer diversity remain incompletely understood.
Purpose of the Study:
- To investigate how TCR V-region bias influences TCRαβ heterodimer selection and diversity.
- To elucidate the structural basis for TCR recognition of pMHCI complexes.
Main Methods:
- Analysis of the D(b)PA(224)-specific TCR repertoire in influenza A virus-infected mice.
- Structural characterization of a TCRαβ-pMHCI complex.
- Retrovirus-mediated expression of TCR Vα-chains.
Main Results:
- A bias towards the TRBV29 gene segment and a specific CDR3β length (6 amino acids) was observed in the D(b)PA(224)-specific TCR repertoire.
- Despite V-region bias, a wide diversity of CDR3β sequences was utilized.
- Structural analysis revealed that CDR3α side chains interacted with peptides, while the CDR3β backbone contacted peptides, highlighting the importance of CDR3β length over sequence for recognition.
Conclusions:
- TCR V-region bias, particularly CDR3β length, contributes to maintaining pMHCI specificity while allowing for sequence diversity.
- Constraining TCR Vα-chain pairing influences TCRαβ heterodimer formation and CDR3β diversity within a preferred TCRVβ spectrum.
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