The Immunodominance Of Cd4 T Cell Epitopes Is Peptide Intrinsic

Overview

Establishment of an immune response that is focused on a limited number of peptide determinants expressed by a complex antigen or pathogen is a phenomenon known as immunodominance. For CD4 T cells, many of the mechanisms used to explain this selectivity suggest that events related to antigen processing play a major role in determining a peptide's ability to recruit CD4 T cells. However, more recent data have revealed that an intrinsic biochemical property of the peptide---the kinetic stability of the peptide:MHC ...
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Overview

Establishment of an immune response that is focused on a limited number of peptide determinants expressed by a complex antigen or pathogen is a phenomenon known as immunodominance. For CD4 T cells, many of the mechanisms used to explain this selectivity suggest that events related to antigen processing play a major role in determining a peptide's ability to recruit CD4 T cells. However, more recent data have revealed that an intrinsic biochemical property of the peptide---the kinetic stability of the peptide:MHC class II complex---both predicts and controls CD4 T cell immunodominance. At the initiation of these studies, we hypothesized that peptide stability from MHC class II is the principle factor in determining the immunogenicity of a given peptide. Those peptides that have a very stable interaction with its presenting MHC class II molecule will not only have an advantage during the processing of antigen but also in the events after peptide presentation at the surface of the antigen-bearing cell. Thus selecting for CD4 T cells that recognize only very persistent peptide:class II complexes for the final specificity of the CD4 T cell repertoire after antigen challenge. The results herein show that the immunodominant heirarchy of peptides contained in complex antigens is independent of molecular context, competing peptides and epitope availability and is principally due to an intrinsic factor of the peptide, based upon the stability of that peptide for MHC class II molecules. Additionally, when antigen processing is bypassed, low stability peptide:class II complexes were capable of supporting the initial priming and expansion of CD4 T cells but the expansion becomes strikingly aborted in the presence of competitive T cell responses to unrelated dominant peptides. These findings suggest that the immune system has adopted multiple independent mechanisms to select a CD4 T cell repertoire that is focused on long-lived peptide:class II complexes during a response to invading pathogens or vaccine- induced immune responses.
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Product Details

  • ISBN-13: 9781243682529
  • Publisher: BiblioLabsII
  • Publication date: 9/7/2011
  • Pages: 250
  • Product dimensions: 7.44 (w) x 9.69 (h) x 0.53 (d)

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