LEPROSY PATIENTS WITH LEPROMATOUS DISEASE RECOGNIZE CROSS-REACTIVE T-CELL EPITOPES IN THE MYCOBACTERIUM-LEPRAE 10-KD ANTIGEN

T cell responses play a critical role in determining protective respon ses to leprosy. Patients with self-limiting tuberculoid leprosy shaw h igh T cell reactivity, while patients with disseminated lepromatous fo rm of the disease show absent to low levels of T cell reactivity. Sinc e the T cell reactivity of lepromatous patients to purified protein de rivative (PPD), a highly cross-reactive antigen, is similar to that of tuberculoid patients, we queried if lepromatous patients could recogn ize cross-reactive epitopes in Mycobacterium leprae antigens as well. T cell responses were analysed to a recombinant antigen 10-kD (a heat shock cognate protein) which is available from both M. tuberculosis (M T) and M. leprae (ML) and displays 90% identity in its amino acid sequ ence. Lymphoproliferative responses were assessed to ML and MT 10 kD i n newly diagnosed leprosy patients (lepromatous, n = 23; tuberculoid, n = 65). Lepromatous patients showed similar, but low, lymphoprolifera tive responses to ML and MT 10 kD, while tuberculoid patients showed m uch higher responses to ML 10 kD. This suggests that the tuberculoid p atients may be recognizing both species-specific and cross-reactive ep itopes in ML 10 kD, while lepromatous patients may be recognizing only cross-reactive epitopes. This was further supported by linear regress ion analysis. Lepromatous patients showed a high concordance in T cell responses between ML and MT 10 kD (r = 0.658; P < 0.0006) not observe d in tuberculoid patients (r = 0.203; P > 0.1). Identification of cros s-reactive T cell epitopes in M. leprae which could induce protective responses should prove valuable in designing second generation peptide -based vaccines.