TY - JOUR T1 - The immunodominant T-cell epitopes of the mycolyl-transferases of the Antigen 85 complex of M. tuberculosis34076 JF - Front Immunol. Y1 - 2014 A1 - K Huygen KW - a KW - acid KW - Acids KW - Activity KW - ALL KW - Animal KW - Antigens KW - article KW - AS KW - Bacillus KW - Belgium KW - Brussels KW - Cattle KW - Cell KW - Cell Wall KW - Control KW - culture KW - disease KW - Diseases KW - electronic KW - Epitopes KW - families KW - Family KW - health KW - Healthy KW - Human KW - Humans KW - immune response KW - immunology KW - Individuals KW - INFECTION KW - infections KW - Infectious KW - Infectious diseases KW - Institute KW - IS KW - journal KW - M KW - mice KW - MODEL KW - models KW - Mycobacterium KW - Mycobacterium bovis KW - Mycobacterium ulcerans KW - Mycolic Acids KW - Patient KW - patients KW - Peptides KW - production KW - PROGRAM KW - Programs KW - protein KW - Proteins KW - public KW - public health KW - Public-health KW - response KW - Responses KW - result KW - results KW - REVIEW KW - secretion KW - Service KW - study KW - Synthetic KW - Tuberculosis KW - vaccine KW - WIV-ISP AB - The Ag85 complex is a 30-32 kDa family of three proteins (Ag85A, Ag85B, and Ag85C), which all three possess enzymatic mycolyl-transferase activity involved in the coupling of mycolic acids to the arabinogalactan of the cell wall and in the biogenesis of cord factor. By virtue of their strong potential to induce Th1-type immune responses, important for the control of intracellular infections, members of the Ag85 family rank among the most promising TB vaccine candidate antigens. Ag85A and Ag85B, initially purified from Mycobacterium bovis bacillus Calmette-Guerin (BCG)/Mycobacterium tuberculosis culture filtrate respectively, induce strong T-cell proliferation and IFN-gamma production in most healthy individuals latently infected with M. tuberculosis and in BCG-vaccinated mice and humans but not in tuberculosis patients. Members of the Ag85 complex are highly conserved in other mycobacterial species. Mice and humans infected with Mycobacterium ulcerans or cattle infected with M. bovis or Mycobacterium avium subsp. paratuberculosis also show strong T-cell responses to this protein family. Using synthetic overlapping peptides, bio-informatic prediction programs and tetramer-binding studies, a number of immunodominant CD4(+) and CD8(+) T-cell epitopes have been identified in experimental animal models as well as in humans, using proliferation and Th1 cytokine secretion as main read-outs. The results from these studies are summarized in this review VL - 5 U1 - 34076 M3 - http://dx.doi.org/10.3389/fimmu.2014.00321 ER -