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Infection and Immunity, November 1999, p. 5567-5572, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Deglycosylation of the 45/47-Kilodalton Antigen Complex of Mycobacterium tuberculosis Decreases Its Capacity To Elicit In Vivo or In Vitro Cellular Immune Responses

Félix Romain,1 Cynthia Horn,1 Pascale Pescher,1 Abdelkader Namane,2 Michel Riviere,3 Germain Puzo,3 Octavian Barzu,2 and Gilles Marchal1,*

Unité de Physiopathologie de l'Infection1 and Laboratoire de Chimie Structurale des Macromolécules,2 Institut Pasteur, 75724 Paris Cedex 15, and Institut de Pharmacologie et de Biologie Structurale, CNRS, 31077 Toulouse Cedex,3 France

Received 1 April 1999/Returned for modification 17 May 1999/Accepted 9 August 1999

A protection against a challenge with Mycobacterium tuberculosis is induced by previous immunization with living attenuated mycobacteria, usually bacillus Calmette-Guérin (BCG). The 45/47-kDa antigen complex (Apa) present in culture filtrates of BCG of M. tuberculosis has been identified and isolated based on its ability to interact mainly with T lymphocytes and/or antibodies induced by immunization with living bacteria. The protein is glycosylated. A large batch of Apa was purified from M. tuberculosis culture filtrate to determine the extent of glycosylation and its role on the expression of the immune responses. Mass spectrometry revealed a spectrum of glycosylated molecules, with the majority of species bearing six, seven, or eight mannose residues (22, 24, and 17%, respectively), while others three, four, or five mannoses (5, 9, and 14%, respectively). Molecules with one, two, or nine mannoses were rare (1.5, 3, and 3%, respectively), as were unglycosylated species (in the range of 1%). To eliminate the mannose residues linked to the protein, the glycosylated Apa molecules were chemically or enzymatically treated. The deglycosylated antigen was 10-fold less active than native molecules in eliciting delayed-type hypersensitivity reactions in guinea pigs immunized with BCG. It was 30-fold less active than native molecules when assayed in vitro for its capacity to stimulate T lymphocytes primed in vivo. The presence of the mannose residues on the Apa protein was essential for the antigenicity of the molecules in T-cell-dependent immune responses in vitro and in vivo.

* Corresponding author. Mailing address: Unité de Physiopathologie de l'Infection, Institut Pasteur, 25 rue du Dr Roux, 75724 Paris Cedex 15, France. Phone: (33) 1 45 68 86 68. Fax: (33) 1 40 61 33 32. E-mail: gmarchal{at}pasteur.fr.

Infection and Immunity, November 1999, p. 5567-5572, Vol. 67, No. 11
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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