Difference in TB10.4 T-cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis.
Most novel vaccines against infectious diseases are based on recombinant Ag; however, only few studies have compared Ag-specific immune responses induced by natural infection with that induced by the same Ag in a recombinant form. Here, we studied the epitope recognition pattern of the tuberculosis vaccine Ag, TB10.4, in a recombinant form, or when expressed by the pathogen Mycobacterium tuberculosis (M.tb), or by the current anti-tuberculosis vaccine, Mycobacterium bovis BCG. We showed that BCG and M.tb induced a similar CD4+ T-cell specific TB10.4 epitope-pattern, which differed completely from that induced by recombinant TB10.4. This difference was not due to post-translational modifications of TB10.4 or because TB10.4 is secreted from BCG and M.tb as a complex with Rv0287. In addition, BCG and TB10.4/CAF01 were both taken up by DC and macrophages in vivo, and in vitro uptake experiments revealed that both TB10.4 and BCG were transported to Lamp+-compartments. BCG and TB10.4 however, were directed to different types of Lamp+-compartments in the same APC, which may lead to different epitope recognition patterns. In conclusion, we show that different vectors can induce completely different recognition of the same protein.
Billeskov
Rolf
R
Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark. rob@ssi.dk
Grandal
Michael V
MV
Poulsen
Christian
C
Christensen
Jan P
JP
Winther
Nathalie
N
Vingsbo-Lundberg
Carina
C
Hoang
Truc T K T
TT
van Deurs
Bo
B
Song
Young-Hwa
YH
Aagaard
Claus
C
Andersen
Peter
P
Dietrich
Jes
J
D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology* / Q000493:pharmacokinetics; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D003433:Crosses, Genetic; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D007113:Immunity, Innate; D007114:Immunization; D007371:Interferon-gamma / Q000378:metabolism; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009504:Neutrophils / Q000276:immunology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000493:pharmacokinetics; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D014376:Tuberculosis / Q000276:immunology / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology* / Q000493:pharmacokinetics; D014614:Vaccines, Synthetic / Q000276:immunology
D000942:Antigens, Bacterial; D001500:BCG Vaccine; D002352:Carrier Proteins; D018984:Epitopes, T-Lymphocyte; D009842:Oligopeptides; D011993:Recombinant Fusion Proteins; C501710:TB10.4 antigen, Mycobacterium tuberculosis; D032581:Tuberculosis Vaccines; D014614:Vaccines, Synthetic; D007371:Interferon-gamma