A 35-KILODALTON PROTEIN IS A MAJOR TARGET OF THE HUMAN IMMUNE-RESPONSE TO MYCOBACTERIUM-LEPRAE

The control of leprosy will be facilitated by the identification of ma jor Mycobacterium leprae-specific antigens which mirror the immune res ponse to the organism across the leprosy spectrum. We have investigate d the host response to a 35-kDa protein of M. leprae. Recombinant 35-k Da protein purified from Mycobacterium smegmatis resembled the native antigen in the formation of multimeric complexes and binding by monocl onal antibodies and sera from leprosy patients. These properties were not shared by two forms of 35-kDa protein purified from Escherichia co il. The M. smegmatis-derived 35-kDa protein stimulated a gamma interfe ron-secreting T-cell proliferative response in the majority of pauciba cillary leprosy patients and healthy contacts of leprosy patients test ed. 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 t uberculosis patients recognized the antigen. This specificity was conf irmed in guinea pigs, with the 35-kDa protein eliciting strong delayed -type hypersensitivity in M. leprae-sensitized animals but not in thos e sensitized with Mycobacterium tuberculosis or Mycobacterium bovis BC G. Therefore, the M. leprae 35-kDa protein appears to he a major and r elatively specific target of the human immune response to M. leprae an d is a potential component of a diagnostic test to detect exposure to leprosy or a vaccine to combat the disease.