ABSTRACT
Zaire ebolavirus (EBOV) is a highly pathogenic filovirus which can result in Ebola virus disease (EVD); a serious medical condition that presents as flu like symptoms but then often leads to more serious or fatal outcomes. The 2013-16 West Africa epidemic saw an unparalleled number of cases. Here we show characterisation and identification of T cell epitopes in surviving patients from Guinea to the EBOV glycoprotein. We perform interferon gamma (IFNγ) ELISpot using a glycoprotein peptide library to identify T cell epitopes and determine the CD4+ or CD8+ T cell component response. Additionally, we generate data on the T cell phenotype and measure polyfunctional cytokine secretion by these antigen specific cells. We show candidate peptides able to elicit a T cell response in EBOV survivors and provide inferred human leukocyte antigen (HLA) allele restriction. This data informs on the long-term T cell response to Ebola virus disease and highlights potentially important immunodominant peptides.
Subject(s)
Ebolavirus/immunology , Epitopes, T-Lymphocyte/immunology , Glycoproteins/immunology , Hemorrhagic Fever, Ebola/immunology , T-Lymphocytes/immunology , Africa, Western/epidemiology , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Ebolavirus/genetics , Enzyme-Linked Immunospot Assay , Epidemics , Glycoproteins/genetics , Hemorrhagic Fever, Ebola/epidemiology , Humans , Immunity, Cellular , Interferon-gamma , SurvivorsSubject(s)
Leukemia, Hairy Cell/complications , Leukemia, Hairy Cell/diagnosis , T-Lymphocytes/immunology , Tuberculosis/complications , Tuberculosis/diagnosis , Aged , Antigens, Bacterial/immunology , Bacterial Proteins/immunology , Cell Count , Female , Humans , Leukemia, Hairy Cell/microbiology , Molecular Diagnostic Techniques , Mycobacterium tuberculosis/immunology , Mycobacterium tuberculosis/isolation & purification , Sensitivity and Specificity , Tuberculin Test , Tuberculosis/bloodABSTRACT
Knowledge of the prevalence of latent Mycobacterium tuberculosis infection is crucial for effective tuberculosis control, but tuberculin skin test surveys have major limitations, including poor specificity because of the broad antigenic cross-reactivity of tuberculin. The M. tuberculosis RD1 genomic segment encodes proteins, such as early secretory antigenic target (ESAT)-6, that are absent from M. bovis bacille Calmette-Guérin (BCG) and most environmental mycobacteria. We recently identified circulating ESAT-6-specific T cells as an accurate marker of M. tuberculosis infection. Here, interferon-gamma-secreting T cells specific for peptides derived from ESAT-6 and a second RD1 gene product, CFP10, were enumerated in 100 prospectively recruited healthy adults in Bombay (Mumbai), India. Eighty percent responded to >/=1 antigen, and many donors had high frequencies of T cells that were specific for certain immunodominant peptides. In contrast, of 40 mostly BCG-vaccinated, United Kingdom-resident healthy adults, none responded to either antigen. This study suggests an 80% prevalence of latent M. tuberculosis infection in urban India.
