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A 35-kilodalton protein is a major target of the human immune response to Mycobacterium leprae
J A Triccas1, P W Roche, N Winter
1Centenary Institute of Cancer Medicine and Cell Biology, Newtown, New South Wales, Australia.
Abstract:
The control of leprosy will be facilitated by the identification of major Mycobacterium leprae-specific antigens which mirror the immune response to the organism across the leprosy spectrum. We have investigated the host response to a 35-kDa protein of M. leprae. Recombinant 35-kDa protein purified from Mycobacterium smegmatis resembled the native antigen in the formation of multimeric complexes and binding by monoclonal antibodies and sera from leprosy patients. These properties were not shared by two forms of 35-kDa protein purified from Escherichia coli. The M. smegmatis-derived 35-kDa protein stimulated a gamma interferon-secreting T-cell proliferative response in the majority of paucibacillary leprosy patients and healthy contacts of leprosy patients tested. Cellular responses to the protein in patients with multibacillary leprosy were weak or absent, consistent with hyporesponsiveness to M. leprae characteristic of this form of the disease. Almost all leprosy patients and contacts recognized the 35-kDa protein by either a T-cell proliferative or an immunoglobulin G antibody response, whereas few tuberculosis patients recognized the antigen. This specificity was confirmed in guinea pigs, with the 35-kDa protein eliciting strong delayed-type hypersensitivity in M. leprae-sensitized animals but not in those sensitized with Mycobacterium tuberculosis or Mycobacterium bovis BCG. Therefore, the M. leprae 35-kDa protein appears to be a major and relatively specific target of the human immune response to M. leprae and is a potential component of a diagnostic test to detect exposure to leprosy or a vaccine to combat the disease.
Insights
A specific 35-kDa protein from Mycobacterium leprae, derived from M. smegmatis, effectively mirrors the immune response in leprosy patients. This antigen shows promise for developing new leprosy diagnostic tests and vaccines.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Leprosy control requires identifying Mycobacterium leprae-specific antigens that reflect the immune response spectrum.
- Understanding host responses to M. leprae antigens is crucial for diagnostic and therapeutic advancements.
Purpose of the Study:
- To investigate the host immune response to a 35-kDa protein of Mycobacterium leprae.
- To evaluate the potential of this M. leprae antigen as a diagnostic marker or vaccine component.
Main Methods:
- Production and purification of recombinant 35-kDa M. leprae protein from Mycobacterium smegmatis and Escherichia coli.
- Assessment of antigen properties, including multimeric complex formation and antibody binding.
- Evaluation of T-cell proliferative responses and immunoglobulin G antibody production in leprosy patients, contacts, and tuberculosis patients.
- Delayed-type hypersensitivity testing in guinea pigs sensitized with different mycobacterial species.
Main Results:
- The M. smegmatis-derived 35-kDa protein exhibited properties similar to the native antigen and was recognized by sera from leprosy patients.
- A significant T-cell proliferative response to the M. smegmatis-derived protein was observed in paucibacillary leprosy patients and healthy contacts, but not in multibacillary patients.
- The 35-kDa protein elicited specific T-cell and antibody responses in most leprosy patients and contacts, with minimal recognition by tuberculosis patients.
- Guinea pig studies confirmed the antigen's specificity for M. leprae sensitization.
Conclusions:
- The M. leprae 35-kDa protein derived from M. smegmatis is a major and specific target of the human immune response to M. leprae.
- This antigen holds potential for use in diagnostic tests to detect leprosy exposure and in the development of a leprosy vaccine.
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