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

Rolf Billeskov; Michael V Grandal; Christian Poulsen; Jan P Christensen; Nathalie Winther; Carina Vingsbo-Lundberg; Truc T K T Hoang; Bo van Deurs; Young-Hwa Song; Claus Aagaard; Peter Andersen; Jes Dietrich

doi:10.1002/eji.200939830

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

Rolf Billeskov, Michael V Grandal, Christian Poulsen, Jan P Christensen, Nathalie Winther, Carina Vingsbo-Lundberg, Truc T K T Hoang, Bo van Deurs, Young-Hwa Song, Claus Aagaard, Peter Andersen, Jes Dietrich

21 Citations (Scopus)

Abstract

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.

Original language	English
Journal	European Journal of Immunology
ISSN	0014-2980
DOIs	https://doi.org/10.1002/eji.200939830
Publication status	Published - May 2010

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Billeskov, R., Grandal, M. V., Poulsen, C., Christensen, J. P., Winther, N., Vingsbo-Lundberg, C., Hoang, T. T. K. T., van Deurs, B., Song, Y-H., Aagaard, C., Andersen, P., & Dietrich, J. (2010). Difference in TB10.4 T-cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis. European Journal of Immunology. https://doi.org/10.1002/eji.200939830

Billeskov, R, Grandal, MV, Poulsen, C, Christensen, JP, Winther, N, Vingsbo-Lundberg, C, Hoang, TTKT, van Deurs, B, Song, Y-H, Aagaard, C, Andersen, P & Dietrich, J 2010, 'Difference in TB10.4 T-cell epitope recognition following immunization with recombinant TB10.4, BCG or infection with Mycobacterium tuberculosis', European Journal of Immunology. https://doi.org/10.1002/eji.200939830

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

abstract = "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.",

author = "Rolf Billeskov and Grandal, {Michael V} and Christian Poulsen and Christensen, {Jan P} and Nathalie Winther and Carina Vingsbo-Lundberg and Hoang, {Truc T K T} and {van Deurs}, Bo and Young-Hwa Song and Claus Aagaard and Peter Andersen and Jes Dietrich",

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AU - Billeskov, Rolf

AU - Grandal, Michael V

AU - Poulsen, Christian

AU - Christensen, Jan P

AU - Winther, Nathalie

AU - Vingsbo-Lundberg, Carina

AU - Hoang, Truc T K T

AU - van Deurs, Bo

AU - Song, Young-Hwa

AU - Aagaard, Claus

AU - Andersen, Peter

AU - Dietrich, Jes

PY - 2010/5

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N2 - 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.

AB - 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.

U2 - 10.1002/eji.200939830

DO - 10.1002/eji.200939830

M3 - Journal article

C2 - 20186878

SN - 0014-2980

JO - European Journal of Immunology

JF - European Journal of Immunology

ER -

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

Abstract

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