This Article Full Text Full Text (PDF) Other Versions of this Article: IAI.01990-06v1 75/6/2914    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Geluk, A. Articles by Klein, M. R. Search for Related Content PubMed PubMed Citation Articles by Geluk, A. Articles by Klein, M. R.

 Previous Article  |  Next Article 

Infection and Immunity, June 2007, p. 2914-2921, Vol. 75, No. 6
0019-9567/07/$08.00+0     doi:10.1128/IAI.01990-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

T-Cell Recognition of the HspX Protein of Mycobacterium tuberculosis Correlates with Latent M. tuberculosis Infection but Not with M. bovis BCG Vaccination

Department of Infectious Diseases and Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, 2300 RC Leiden, The Netherlands

Received 19 December 2006/ Returned for modification 12 February 2007/ Accepted 14 March 2007

During stationary growth or in vitro conditions mimicking relevant aspects of latency, the HspX protein (Rv2031c) is specifically upregulated by Mycobacterium tuberculosis. In this study we compared T-cell responses against HspX and the secreted M. tuberculosis protein Ag85B (Rv1886c) in tuberculosis (TB) patients, tuberculin skin test-positive individuals, M. bovis BCG-vaccinated individuals, and healthy negative controls. Gamma interferon responses to HspX were significantly higher in M. tuberculosis-exposed individuals than in M. tuberculosis-unexposed BCG vaccinees. In contrast, no such differences were found with respect to T-cell responses against Ag85B. Therefore, BCG-based vaccines containing relevant fragments of HspX may induce improved responses against this TB latency antigen. To identify relevant major histocompatibility complex class I- and class II-restricted HspX-specific T-cell epitopes, we immunized HLA-A2/K^b and HLA-DR3.Ab⁰ transgenic (tg) mice with HspX. Two new T-cell epitopes were identified, p91-105 and p31-50, restricted via HLA-A*0201 and HLA-DRB1*0301, respectively. These epitopes were recognized by human T cells as well, underlining the relevance of HspX T-cell recognition both in vivo and in vitro. In line with the data in humans, BCG immunization of both tg strains did not lead to T-cell responses against HspX-derived epitopes, whereas nonlatency antigens were efficiently recognized. These data support the notion that BCG vaccination per se does not induce T-cell responses against the latency antigen, HspX. Thus, we suggest that subunit vaccines incorporating HspX and/or other latency antigens, as well as recombinant BCG strains expressing latency antigens need to be considered as new vaccines against TB.

Published ahead of print on 26 March 2007.

Editor: J. L. Flynn

This article has been cited by other articles:

• Lin, M. Y., Geluk, A., Smith, S. G., Stewart, A. L., Friggen, A. H., Franken, K. L. M. C., Verduyn, M. J. C., van Meijgaarden, K. E., Voskuil, M. I., Dockrell, H. M., Huygen, K., Ottenhoff, T. H. M., Klein, M. R. (2007). Lack of Immune Responses to Mycobacterium tuberculosis DosR Regulon Proteins following Mycobacterium bovis BCG Vaccination. Infect. Immun. 75: 3523-3530 [Abstract] [Full Text]