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

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.

• Authors: 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
• Journal: Infection and immunity (Infect Immun) Vol. 82 Issue 1 Pg. 124-31 (Jan 2014) ISSN: 1098-5522 [Electronic] United States
• PMID: 24126518 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antigens, Bacterial
• Bacterial Proteins
• Epitopes, T-Lymphocyte
• Immunoglobulin G
• Interleukin-5
• Interferon-gamma

Topics

• Acute Disease
• Antigens, Bacterial (analysis)
• Bacterial Proteins (analysis)
• Brucella melitensis (immunology)
• Brucellosis (immunology)
• CD4-Positive T-Lymphocytes (immunology)
• Chronic Disease
• Cohort Studies
• Epitopes, T-Lymphocyte (immunology)
• Humans
• Immunity, Cellular (immunology)
• Immunoglobulin G (immunology)
• Interferon-gamma (metabolism)
• Interleukin-5 (metabolism)
• Microarray Analysis (methods)
• Peru