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Brucella melitensis T cell epitope recognition in humans with brucellosis in Peru

  • Author(s): Cannella, AP
  • Arlehamn, CSL
  • Sidney, J
  • Patra, KP
  • Torres, K
  • Tsolis, RM
  • Liang, L
  • Felgner, PL
  • Saito, M
  • Gotuzzo, E
  • Gilman, RH
  • Sette, A
  • Vinetz, JM
  • et al.

Published Web Location

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3911835/
No data is associated with this publication.
Abstract

Brucella melitensis, one of the causative agents of human brucellosis, causes acute, chronic, and relapsing infection. While T cell immunity in brucellosis has been extensively studied in mice, no recognized human T cell epitopes that might provide new approaches to classifying and prognosticating B. melitensis infection have ever been delineated. Twenty-seven pools of 500 major histocompatibility complex class II (MHC-II) restricted peptides were created by computational prediction of promiscuous MHC-II CD4+ T cell derived from the top 50 proteins recognized by IgG in human sera on a genome level B. melitensis protein microarray. Gamma interferon (IFN-γ) and interleukin-5 (IL-5) enzyme-linked immunospot (ELISPOT) analyses were used to quantify and compare Th1 and Th2 responses of leukapheresis-obtained peripheral blood mononuclear cells from Peruvian subjects cured after acute infection (n=9) and from patients who relapsed (n=5). Four peptide epitopes derived from 3 B. melitensis proteins (BMEI 1330, a DegP/HtrA protease; BMEII 0029, type IV secretion system component VirB5; and BMEII 0691, a predicted periplasmic binding protein of a peptide transport system) were found repeatedly to produce significant IFN-γ ELISPOT responses in both acute-infection and relapsing patients; none of the peptides distinguished the patient groups. IL-5 responses against the panel of peptides were insignificant. These experiments are the first to systematically identify B. melitensis MHC-II-restricted CD4+ T cell epitopes recognized by the human immune response, with the potential for new approaches to brucellosis diagnostics and understanding the immunopathogenesis related to this intracellular pathogen. © 2014, American Society for Microbiology.

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