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Infection and Immunity, May 2002, p. 2544-2548, Vol. 70, No. 5
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.5.2544-2548.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Identification and Characterization of the ESAT-6 Homologue of Mycobacterium leprae and T-Cell Cross-Reactivity with Mycobacterium tuberculosis

Annemieke Geluk,1* Krista E. van Meijgaarden,1 Kees L. M. C. Franken,1 Yanri W. Subronto,1 Brigitte Wieles,1 Sandra M. Arend,1,2 Elizabeth P. Sampaio,3 Tjitske de Boer,1 William R. Faber,4 Ben Naafs,5 and Tom H. M. Ottenhoff1

Department of Immunohematology and Blood Transfusion,1 Department of Dermatology,5 Department of Infectious Diseases, Leiden University Medical Center, Leiden,2 Department of Dermatology, Amsterdam Medical Center, Amsterdam, The Netherlands,4 Leprosy Laboratory IOC Fiocruz, Rio de Janeiro, Brazil3

Received 24 August 2001/ Returned for modification 4 October 2001/ Accepted 14 January 2002

In this paper we describe identification and characterization of Mycobacterium leprae ESAT-6 (L-ESAT-6), the homologue of M. tuberculosis ESAT-6 (T-ESAT-6). T-ESAT-6 is expressed by all pathogenic strains belonging to the M. tuberculosis complex but is absent from virtually all other mycobacterial species, and it is a promising antigen for immunodiagnosis of tuberculosis (TB). Therefore, we analyzed whether L-ESAT-6 is a similarly powerful tool for the study of leprosy by examining T-cell responses against L-ESAT-6 in leprosy patients, TB patients, and exposed or nonexposed healthy controls from areas where leprosy and TB are endemic and areas where they are not endemic. L-ESAT-6 was recognized by T cells from leprosy patients, TB patients, individuals who had contact with TB patients, and healthy individuals from an area where TB and leprosy are endemic but not by T cells from individuals who were not exposed to M. tuberculosis and M. leprae. Moreover, leprosy patients who were not responsive to M. leprae failed to respond to L-ESAT-6. A very similar pattern was obtained with T-ESAT-6. These results show that L-ESAT-6 is a potent M. leprae antigen that stimulates T-cell-dependent gamma interferon production in a large proportion of individuals exposed to M. leprae. Moreover, our results suggest that there is significant cross-reactivity between T-ESAT-6 and L-ESAT-6, which has implications for the use of ESAT-6 as tool for diagnosis of leprosy and TB in areas where both diseases are endemic.

* Corresponding author. Mailing address: Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. Phone: 31-71-5263800. Fax: 31-71-5216751. E-mail: ageluk{at}lumc.nl.

Editor: S. H. E. Kaufmann

Infection and Immunity, May 2002, p. 2544-2548, Vol. 70, No. 5
0019-9567/02/$04.00+0     DOI: 10.1128/IAI.70.5.2544-2548.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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