This Article Full Text Full Text (PDF) 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 Kamath, A. B. Articles by Behar, S. M. Search for Related Content PubMed PubMed Citation Articles by Kamath, A. B. Articles by Behar, S. M.

The Major Histocompatibility Complex Haplotype Affects T-Cell Recognition of Mycobacterial Antigens but Not Resistance to Mycobacterium tuberculosis in C3H Mice

Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts

Received 10 June 2004/ Returned for modification 27 July 2004/ Accepted 13 August 2004

Both innate and adaptive immunity play an important role in host resistance to Mycobacterium tuberculosis infection. Although several studies have suggested that the major histocompatibility complex (MHC) haplotype affects susceptibility to infection, it remains unclear whether the modulation of T-cell immunity by the MHC locus determines the host's susceptibility to tuberculosis. To determine whether allelic differences in the MHC locus affect the T-cell immune response after M. tuberculosis infection, we infected inbred and H-2 congenic mouse strains by the respiratory route. The H-2 locus has a profound effect on the antigen-specific CD4⁺-T-cell response after M. tuberculosis infection. CD4⁺ T cells from infected mice of the H-2^b haplotype produced more gamma interferon (IFN-) after in vitro stimulation with mycobacterial antigens than mice of the H-2^k haplotype. A higher level of IFN- was also detected in bronchoalveolar lavage fluid from infected mice of the H-2^b haplotype. Furthermore, C3.SW-H2^b/SnJ mice generate and recruit activated T cells to the lung after infection. Despite a robust immune response, C3.SW-H2^b/SnJ mice succumbed to infection early and were similarly susceptible to infection as other C3H (H-2^k) substrains. These results suggest that although the MHC haplotype has a profound impact on the T-cell recognition of M. tuberculosis antigens, the susceptibility of C3H mice to infection is MHC independent.

Editor: J. B. Bliska

This article has been cited by other articles:

• Yan, B.-S., Pichugin, A. V., Jobe, O., Helming, L., Eruslanov, E. B., Gutierrez-Pabello, J. A., Rojas, M., Shebzukhov, Y. V., Kobzik, L., Kramnik, I. (2007). Progression of Pulmonary Tuberculosis and Efficiency of Bacillus Calmette-Guerin Vaccination Are Genetically Controlled via a Common sst1-Mediated Mechanism of Innate Immunity. J. Immunol. 179: 6919-6932 [Abstract] [Full Text]  
• Kamath, A., Woodworth, J. S.M., Behar, S. M. (2006). Antigen-Specific CD8+ T Cells and the Development of Central Memory during Mycobacterium tuberculosis Infection. J. Immunol. 177: 6361-6369 [Abstract] [Full Text]  
• Pichugin, A. V., Petrovskaya, S. N., Apt, A. S. (2006). H2 complex controls CD4/CD8 ratio, recurrent responsiveness to repeated stimulations, and resistance to activation-induced apoptosis during T cell response to mycobacterial antigens. J. Leukoc. Biol. 79: 739-746 [Abstract] [Full Text]  
• Smith, I., Nathan, C., Peavy, H. H. (2005). Progress and New Directions in Genetics of Tuberculosis: An NHLBI Working Group Report. Am. J. Respir. Crit. Care Med. 172: 1491-1496 [Abstract] [Full Text]  
• Kamath, A. B., Behar, S. M. (2005). Anamnestic Responses of Mice following Mycobacterium tuberculosis Infection. Infect. Immun. 73: 6110-6118 [Abstract] [Full Text]