Immunodominance of CD4 T cells to foreign antigens is peptide intrinsic and independent of molecular context: implications for vaccine design.

The Journal of Immunology : Official Journal of the American Association of Immunologists
Jason M WeaverAndrea J Sant

Abstract

Immunodominance refers to the restricted peptide specificity of T cells that are detectable after an adaptive immune response. For CD4 T cells, many of the mechanisms used to explain this selectivity suggest that events related to Ag processing play a major role in determining a peptide's ability to recruit CD4 T cells. Implicit in these models is the prediction that the molecular context in which an antigenic peptide is contained will impact significantly on its immunodominance. In this study, we present evidence that the selectivity of CD4 T cell responses to peptides contained within protein Ags is not detectably influenced by the location of the peptide in a given protein or the primary sequence of the protein that bears the test peptide. We have used molecular approaches to change the location of peptides within complex protein Ags and to change the flanking sequences that border the peptide epitope to now include a protease site, and find that immunodominance or crypticity of a peptide observed in its native protein context is preserved. Collectively, these results suggest immunodominance of peptides contained in complex Ags is due to an intrinsic factor of the peptide, based upon the affinity of that peptide for MHC clas...Continue Reading

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Citations

Aug 4, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michael ReiserReinhold Schirmbeck
Jun 21, 2020·Journal for Immunotherapy of Cancer·Victoria A BrentvilleLindy G Durrant
Apr 25, 2012·International Immunology·David R KroegerPeter A Bretscher
Apr 3, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Francisco A ChavesAndrea J Sant
Sep 6, 2017·The Journal of Pharmacy and Pharmacology·Amy S Rosenberg, Zuben E Sauna
Jun 27, 2018·Immunological Reviews·Andrea J SantKatherine A Richards
Oct 23, 2019·Vaccines·Shubhranshu ZutshiBhaskar Saha
Feb 10, 2009·Immunologic Research·Jason M Weaver, Andrea J Sant
Sep 10, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Michel LéonettiGervaise Moine
Jan 19, 2016·Frontiers in Microbiology·Stephanie AscoughDaniel M Altmann
Jul 28, 2015·International Journal of Immunogenetics·P Oyarzun, B Kobe
May 9, 2009·Proceedings of the National Academy of Sciences of the United States of America·Jason M WeaverAndrea J Sant
Jan 12, 2021·Computational and Structural Biotechnology Journal·Léa V ZinsliMathias Schmelcher
Sep 17, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Meng LiHaipeng Liu

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