CD4+ T cell epitopes of FliC conserved between strains of Burkholderia: Implications for vaccines against melioidosis and cepacia complex in cystic fibrosis

Julie A. Musson, Catherine J. Reynolds, Darawan Rinchai, Arnone Nithichanon, Prasong Khaenam, Emmanuel Favry, Natasha Spink, Karen K.Y. Chu, Anthony De Soyza, Gregory J. Bancroft, Ganjana Lertmemongkolchai, Bernard Maillere, Rosemary J. Boyton, Daniel M. Altmann, John H. Robinson

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Abstract

Burkholderia pseudomallei is the causative agent of melioidosis characterized by pneumonia and fatal septicemia and prevalent in Southeast Asia. Related Burkholderia species are strong risk factors of mortality in cystic fibrosis (CF). The B. pseudomallei flagellar protein FliC is strongly seroreactive and vaccination protects challenged mice. We assessed B. pseudomallei FliC peptide binding affinity to multiple HLA class II alleles and then assessed CD4 T cell immunity in HLA class II transgenic mice and in seropositive individuals in Thailand. T cell hybridomas were generated to investigate cross-reactivity between B. pseudomallei and the related Burkholderia species associated with Cepacia Complex CF. B. pseudomallei FliC contained several peptide sequences with ability to bind multiple HLA class II alleles. Several peptides were shown to encompass strong CD4 T cell epitopes in B. pseudomallei-exposed individuals and in HLA transgenic mice. In particular, the p38 epitope is robustly recognized by CD4 T cells of seropositive donors across diverse HLA haplotypes. T cell hybridomas against an immunogenic B. pseudomallei FliC epitope also cross-reacted with orthologous FliC sequences from Burkholderia multivorans and Burkholderia cenocepacia, important pathogens in CF. Epitopes within FliC were accessible for processing and presentation from live or heat-killed bacteria, demonstrating that flagellin enters the HLA class II Ag presentation pathway during infection of macrophages with B. cenocepacia. Collectively, the data support the possibility of incorporating FliC T cell epitopes into vaccination programs targeting both at-risk individuals in B. pseudomallei endemic regions as well as CF patients.

Original languageEnglish
Pages (from-to)6041-6049
Number of pages9
JournalJournal of Immunology
Volume193
Issue number12
DOIs
Publication statusPublished - 1 Jan 2014
Externally publishedYes

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ASJC Scopus subject areas

  • Immunology

Cite this

Musson, J. A., Reynolds, C. J., Rinchai, D., Nithichanon, A., Khaenam, P., Favry, E., Spink, N., Chu, K. K. Y., De Soyza, A., Bancroft, G. J., Lertmemongkolchai, G., Maillere, B., Boyton, R. J., Altmann, D. M., & Robinson, J. H. (2014). CD4+ T cell epitopes of FliC conserved between strains of Burkholderia: Implications for vaccines against melioidosis and cepacia complex in cystic fibrosis. Journal of Immunology, 193(12), 6041-6049. https://doi.org/10.4049/jimmunol.1402273