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

Anthony P. Cannella, Cecilia S Lindestam Arlehamn, John Sidney, Kailash P. Patra, Katherine Torres, Renee M Tsolis, Li Liang, Philip L. Felgner, Mayuko Saito, Eduardo Gotuzzo, Robert H. Gilman, Alessandro Sette, Joseph M. Vinetz

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)124-131
Number of pages8
JournalInfection and Immunity
Volume82
Issue number1
DOIs
StatePublished - Jan 2014

Fingerprint

Brucella melitensis
Peru
T-Lymphocyte Epitopes
Brucellosis
Major Histocompatibility Complex
Peptides
Interleukin-5
Infection
Periplasmic Binding Proteins
Leukapheresis
T-Lymphocytes
Protein Array Analysis
Enzymes
Interferons
Interferon-gamma
Epitopes
Immunity
Blood Cells
Proteins
Immunoglobulin G

ASJC Scopus subject areas

  • Immunology
  • Microbiology
  • Parasitology
  • Infectious Diseases

Cite this

Cannella, A. P., Arlehamn, C. S. L., Sidney, J., Patra, K. P., Torres, K., Tsolis, R. M., ... Vinetz, J. M. (2014). Brucella melitensis T cell epitope recognition in humans with brucellosis in Peru. Infection and Immunity, 82(1), 124-131. https://doi.org/10.1128/IAI.00796-13

Brucella melitensis T cell epitope recognition in humans with brucellosis in Peru. / Cannella, Anthony P.; Arlehamn, Cecilia S Lindestam; Sidney, John; Patra, Kailash P.; Torres, Katherine; Tsolis, Renee M; Liang, Li; Felgner, Philip L.; Saito, Mayuko; Gotuzzo, Eduardo; Gilman, Robert H.; Sette, Alessandro; Vinetz, Joseph M.

In: Infection and Immunity, Vol. 82, No. 1, 01.2014, p. 124-131.

Research output: Contribution to journalArticle

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 2014, 'Brucella melitensis T cell epitope recognition in humans with brucellosis in Peru', Infection and Immunity, vol. 82, no. 1, pp. 124-131. https://doi.org/10.1128/IAI.00796-13
Cannella, Anthony P. ; Arlehamn, Cecilia S Lindestam ; Sidney, John ; Patra, Kailash P. ; Torres, Katherine ; Tsolis, Renee M ; Liang, Li ; Felgner, Philip L. ; Saito, Mayuko ; Gotuzzo, Eduardo ; Gilman, Robert H. ; Sette, Alessandro ; Vinetz, Joseph M. / Brucella melitensis T cell epitope recognition in humans with brucellosis in Peru. In: Infection and Immunity. 2014 ; Vol. 82, No. 1. pp. 124-131.
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