Difference in TB10.4 T-cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis

被引：23

作者：

Billeskov, Rolf ^{[1
,2
]}

Grandal, Michael V. ^{[3
]}

Poulsen, Christian ^{[4
]}

Christensen, Jan P. ^{[2
]}

Winter, Nathalie ^{[5
]}

Vingsbo-Lundberg, Carina ^{[6
]}

Hoang, Truc T. K. T. ^{[1
]}

van Deurs, Bo ^{[3
]}

Song, Young-Hwa ^{[4
]}

Aagaard, Claus ^{[1
]}

Andersen, Peter ^{[1
]}

Dietrich, Jes ^{[1
]}

机构：

[1] Statens Serum Inst, Dept Infect Dis Immunol, DK-2300 Copenhagen, Denmark

[2] Univ Copenhagen, Inst Int Hlth Immunol & Microbiol, Copenhagen, Denmark

[3] Univ Copenhagen, Dept Cellular & Mol Med, Copenhagen, Denmark

[4] DESY, European Mol Biol Lab, Struct Biol Unit, D-2000 Hamburg, Germany

[5] Inst Pasteur, Mycobacterial Genet Unit, Paris, France

[6] Statens Serum Inst, Dept Antibiot Resistance & Hosp Hyg, DK-2300 Copenhagen, Denmark

来源：

EUROPEAN JOURNAL OF IMMUNOLOGY | 2010年 / 40卷 / 05期

关键词：

Epitopes; Intracellular localization; Subdominant; T cells; Vaccine uptake; DENDRITIC CELLS; COMPLEX-FORMATION; SUBUNIT VACCINE; BOVIS BCG; ESAT-6-CFP-10; COMPLEX; CATIONIC LIPOSOMES; IMMUNE-RESPONSES; ESAT-6; FAMILY; PROTEIN; PROTECTION;

D O I：

10.1002/eji.200939830

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1342 / 1354

页数：13

共 38 条

[1] Protection and Polyfunctional T Cells Induced by Ag85B-TB10.4/IC31® against Mycobacterium tuberculosis Is Highly Dependent on the Antigen Dose [J].