T-CELL RECOGNITION OF MYCOBACTERIAL GROES PEPTIDES IN THAI LEPROSY PATIENTS AND CONTACTS

We report here the mapping of T-cell-stimulatory determinants of the G roES IO-M)a heat shock protein homologues from Mycobacterium leprae an d Mycobacterium tuberculosis, which are known as major immunogens in m ycobacterial infections. Peripheral blood mononuclear cells (PBMC) fro m treated tuberculoid leprosy or lepromatous leprosy patients and from healthy household or hospital staff contacts of the patients were cul tured with 20 16-mer peptides covering the entire sequences of both M, leprae and M, tuberculosis GroES, The total number of recognized pept ides was found to be the largest in family contacts, while responder f requencies to the individual tested peptides varied (5 to 80%! with sp ecificity between the patient and contact groups, Proliferative respon ses to some peptides showed positive or negative associations of low s tatistical significance with DR and DQ alleles, though responses to mo st GroES peptides were genetically permissive, Notably, the sequence o f the 25-40 peptide of M, leprae, but not that of M, tuberculosis, was more frequently stimulatory in tuberculoid leprosy patients than in e ither group of sensitized healthy contacts. This peptide bound to a nu mber of HLA-DR molecules, of which HLA-DRB50101 had the strongest aff inity. The epitope core binding to this allele was localized to the 29 -to-37 sequence, and its key residue was localized to the M, leprae-sp ecific glutamic acid at position 32. This epitope may be of interest f or the development of a blood test- or skin test-based diagnostic reag ent for tuberculoid leprosy, subject to further clinical evaluation in untreated patients.