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CD4+ T Cells Targeting Dominant and Cryptic Epitopes from Bacillus anthracis Lethal Factor.

Stephanie Ascough1, Rebecca J Ingram2, Karen K Y Chu3

  • 1Avian Viral Immunology Group, The Pirbright Institute Pirbright, UK.

Frontiers in Microbiology
|January 19, 2016
PubMed
Summary

Cellular immunity, including T cell responses to Bacillus anthracis lethal factor, is crucial for protection against anthrax. Understanding both dominant and cryptic epitopes is key for developing effective vaccines against this endemic infection.

Keywords:
CD4+HLAanthraxcrypticepitopeimmunodominantlethal factorsubdominant

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Area of Science:

  • Immunology
  • Microbiology
  • Vaccinology

Background:

  • Anthrax, caused by Bacillus anthracis, is a significant global health concern, particularly in developing nations.
  • Adaptive immunity to anthrax has historically focused on humoral responses to bacterial exotoxins.
  • Emerging evidence highlights the critical role of cellular immunity, specifically interferon-gamma (IFNγ) producing CD4+ T cells, in protective memory responses.

Purpose of the Study:

  • To investigate T cell responses to both immunodominant and cryptic epitopes of the Bacillus anthracis lethal factor.
  • To characterize the binding affinities of these epitopes to various HLA-DR alleles.
  • To inform the design of future epitope-based vaccines for broad HLA coverage.

Main Methods:

  • Analysis of T cell responses using IFNγ-ELISpot assays.
  • Immunization of HLA-DR transgenic mice with synthetic peptides and the whole lethal factor protein.
  • In vitro testing of epitope binding to purified HLA-DR molecules.

Main Results:

  • DR1 transgenic mice showed responses to more cryptic epitopes in Domain III compared to other HLA-DR transgenics.
  • Immunodominant epitopes LF457-476 and LF467-487 elicited T cell responses in DR1 and DR15 transgenics, but not DR4.
  • Cryptic epitopes from Domain I exhibited moderate binding affinity to HLA-DR4, but no cryptic epitopes showed high binding across all tested HLA-DR alleles.

Conclusions:

  • T cell responses to anthrax lethal factor are influenced by specific HLA-DR alleles.
  • Both immunodominant and cryptic epitopes contribute to adaptive immunity against Bacillus anthracis.
  • Future anthrax vaccines may benefit from combining both cryptic and immunodominant epitopes for broader immunogenicity across diverse HLA types.