Revealing factors determining immunodominant responses against dominant epitopes.

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  • Additional Information
    • Source:
      Publisher: Springer Verlag Country of Publication: United States NLM ID: 0420404 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1211 (Electronic) Linking ISSN: 00937711 NLM ISO Abbreviation: Immunogenetics Subsets: MEDLINE
    • Publication Information:
      Original Publication: New York, NY : Springer Verlag,
    • Subject Terms:
      Complementarity Determining Regions/*genetics ; Immunodominant Epitopes/*genetics ; Receptors, Antigen, T-Cell/*genetics; Amino Acid Sequence ; CD8-Positive T-Lymphocytes/immunology ; Complementarity Determining Regions/metabolism ; Databases, Factual ; Epitopes/genetics ; Epitopes/immunology ; Epitopes, T-Lymphocyte/immunology ; Humans ; Immunity, Cellular ; Immunodominant Epitopes/immunology ; Lymphocyte Activation ; Molecular Sequence Data ; Receptors, Antigen, T-Cell/immunology ; V(D)J Recombination/genetics
    • Abstract:
      Upon recognition of peptide-MHC complexes by T cell receptors (TCR), the cognate T cells expand and differentiate into effector T cells to generate protective immunity. Despite the fact that any immune response generates a diverse set of TCR clones against a particular epitope, only a few clones are highly expanded in any immune response. Previous studies observed that the highest frequency clones usually control viral infections better than subdominant clones, but the reasons for this dominance among T cell clones are still unclear. Here, we used publicly available TCR amino acid sequences to study which factors determine whether a response becomes immunodominance (ID) per donor; we classified the largest T cell clone as the epitope-specific dominant clone and all the other clones as subdominant responses (SD). We observed a distinctively hydrophobic CDR3 in ID responses against a dominant epitope from influenza A virus, compared to the SD responses. The common V-J combinations were shared between ID and SD responses, suggesting that the biased V-J recombination events are restricted by epitope specificity; thus, the immunodominance is not directly determined by a bias combination of V and J genetic segments. Our findings reveal a close similarity of global sequence properties between dominant and subdominant clones of epitope-specific responses but detectable distinctive amino acid enrichments in ID. Taken together, we believe this first comparative study of immunodominant and subdominant TCR sequences can guide further studies to resolve factors determining the immunodominance of antiviral as well as tumor-specific T cell responses.
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    • Contributed Indexing:
      Keywords: Immunodominance (ID); T cell receptor; VDJdb
    • Accession Number:
      0 (Complementarity Determining Regions)
      0 (Epitopes)
      0 (Epitopes, T-Lymphocyte)
      0 (Immunodominant Epitopes)
      0 (Receptors, Antigen, T-Cell)
    • Publication Date:
      Date Created: 20191208 Date Completed: 20200217 Latest Revision: 20200217
    • Publication Date:
      20231215
    • Accession Number:
      PMC6971151
    • Accession Number:
      10.1007/s00251-019-01134-9
    • Accession Number:
      31811313