Leprosy patients with lepromatous disease recognize cross-reactive T cell epitopes in theMycobacterium leprae10-kD antigen

Abstract

SUMMARYT cell responses play a critical role in determining protective responses to leprosy. Patients with selflimiting tuberculoid leprosy show high T cell reactivity, while patients with disseminated lepromatous form of the disease show absent to low levels of T cell reactivity. Since the T cell reactivity of lepromatous patients to purified protein derivative (PPD), a highly cross-reactive antigen, is similar to that of tuberculoid patients, we queried if lepromatous patients could recognize 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 (MT) and M. leprae (ML) and displays 90% identity in its amino acid sequence. Lymphoproliferative responses were assessed to ML and MT 10 kD in newly diagnosed leprosy patients (lepromatous, n ¼ 23; tuberculoid, n ¼ 65). Lepromatous patients showed similar, but low, lymphoproliferative responses to ML and MT 10 kD, while tuberculoid patients showed much higher responses to ML 10 kD. This suggests that the tuberculoid patients may be recognizing both species-specific and cross-reactive epitopes in ML 10 kD, while lepromatous patients may be recognizing only cross-reactive epitopes. This was further supported by linear regression analysis. Lepromatous patients showed a high concordance in T cell responses between ML and MT 10 kD (r ¼ 0·658; P < 0·0006) not observed in tuberculoid patients (r ¼ 0·203; P > 0·1). Identification of cross-reactive T cell epitopes in M. leprae which could induce protective responses should prove valuable in designing second generation peptide-based vaccines.

Dominant recognition of a cross‐reactive B‐cell epitope in Mycobacterium leprae 10 K antigen by immunoglobulin G1 antibodies across the disease spectrum in leprosy

“…We have looked at two control groups:(i) healthy household contacts of patients with active disease to distinguish antibodies evoked by exposure versus active disease; and(ii) healthy endemic controls to establish baseline antibody levels from exposure to cross‐reactive environmental mycobacteria and BCG vaccination. T‐cell responses have been previously shown to be extremely high in both control groups 17 . Although baseline levels were relatively high for all four IgG subclasses when M. leprae sonicate or ML 65 K was used as antigen, ML 10 K and ML 18 K, on the other hand, showed very low baseline antibody responses in HC.…”

Immune profiling of leprosy and tuberculosis patients to 15‐mer peptides of Mycobacterium leprae and M. tuberculosis GroES in a BCG vaccinated area: implications for development of vaccine and diagnostic reagents

“…T cell responses The N‐terminal end of the ML and MT GroES proteins has several amino acid interchanges (indicated as L peptides). This region has been shown to be recognized by tuberculoid patients in a species‐specific manner 14,19,20 . When T cell responses (solid lines) were analysed to this region, leprosy patients with disseminated lepromatous disease showed a higher number of positive responders to L1–15, while those with localized tuberculoid disease and EC groups showed a greater number of positive responders to L11–25.…”