T-cell-epitope mapping of the major secreted mycobacterial antigen Ag85A in tuberculosis and leprosy.

Détails

ID Serval
serval:BIB_F0235D06972C
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
T-cell-epitope mapping of the major secreted mycobacterial antigen Ag85A in tuberculosis and leprosy.
Périodique
Infection and Immunity
Auteur(s)
Launois P., DeLeys R., Niang M.N., Drowart A., Andrien M., Dierckx P., Cartel J.L., Sarthou J.L., Van Vooren J.P., Huygen K.
ISSN
0019-9567 (Print)
ISSN-L
0019-9567
Statut éditorial
Publié
Date de publication
1994
Volume
62
Numéro
9
Pages
3679-3687
Langue
anglais
Résumé
Lymphoproliferation and gamma interferon (IFN-gamma) secretion in response to 28 overlapping 20-mer synthetic peptides covering the complete sequence of the mature (295-amino-acid) 85A component of the major secreted, fibronectin-binding antigen 85 complex from Mycobacterium tuberculosis and Mycobacterium bovis BCG (MTAg85A) was examined by using peripheral blood mononuclear cell (PBMC) cultures from healthy tuberculin- and lepromin-positive volunteers and from patients with tuberculosis and leprosy. Peptide recognition was largely promiscuous, with a variety of human leukocyte antigen haplotypes reacting to the same peptides. PBMC from all tuberculin-positive subjects reacted to Ag85, and the majority proliferated in response to peptide 6 (amino acids 51 to 70), peptides 13, 14, and 15 (amino acids 121 to 160), or peptides 20 and 21 (amino acids 191 to 220). PBMC from tuberculosis patients demonstrated a variable reactivity to Ag85 and its peptides, and the strongest proliferation was observed against peptide 7 (amino acids 61 to 80). MTAg85A peptides were also recognized by PBMC from healthy lepromin-positive volunteers and paucibacillary leprosy patients (again in a promiscuous manner), but despite a 90% homology between the 85A proteins of M. leprae and M. tuberculosis, the peptides recognized were different. PBMC from lepromin-positive healthy contacts reacted against peptide 2 (amino acids 11 to 30), peptide 5 (amino acids 41 to 60), and peptides 25 and 26 (amino acids 241 to 270). PBMC from paucibacillary patients reacted preferentially against peptide 1 (amino acids 1 to 20) and peptide 5. Multibacillary patients were not reactive to Ag85 or the MT85A peptides. IFN-gamma production was generally detected simultaneously with positive lymphoproliferative responses, although peptide 1 mostly stimulated proliferation and peptides 27 and 28 mostly elicited an IFN-gamma response. In conclusion, regions 41 to 80 and 241 to 295 demonstrated powerful and promiscuous T-cell-stimulatory properties, resulting in proliferative responses and IFN-gamma secretion, respectively, in the majority of reactive subjects tested in this study. These results could be of value in the development of a subunit vaccine for tuberculosis and leprosy.
Mots-clé
Amino Acid Sequence, Antigens, Bacterial/immunology, Epitopes, Humans, Interferon-gamma/biosynthesis, Interferon-gamma/secretion, Leprosy/immunology, Lymphocyte Activation, Molecular Sequence Data, Mycobacterium leprae/immunology, T-Lymphocytes/immunology, Tuberculosis/immunology
Pubmed
Web of science
Création de la notice
28/01/2008 12:06
Dernière modification de la notice
03/03/2018 22:36
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