CD4+ T-cell responses to recombinant hsp65 and hsp18 of M. leprae and their trypsin-digested fragments in leprosy: Diversity in HLA-DR restriction

D. K. Mitra, N. K. Mehra, T. K. Maiti, A. Banerjee, V. Taneja, R. Rajalingam, R. K. Ahuja, B. C. Bhattacharya

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Mycobacterium leprae heat-shock proteins hsp65 and hsp18 have received immense attention as major T-cell target antigens in leprosy. Both of these hsps and their tryptic fragments were characterized for their ability to stimulate CD4+ T cells derived from polar leprosy cases and healthy contacts. The optimal digestion of hsps with trypsin yielded four fragments of hsp65- TDB65-1 (24 kDa), TDB65-2 (18 kDa), TDB65-3 (17 kDa), TDB65-4 (14 kDa)and three of hsp18-TDB18-1 (10 kDa), TDB18-2 (5 kDa), TDB18-3 (3 kDa). While all of these tryptic fragments and undigested hsps triggered CD4+ T cells from tuberculoid (TT) leprosy patients and healthy contacts (SI > 2), only two fragments-TDB65-2 and TDB18-3-were found to be stimulatory in anergic lepromatous (LL) leprosy patients (SI = 5.27 and 3.0, respectively). Blocking studies using allele-specific anti-DR monoclonal antibodies revealed multiple HLA-Dr restriction, with DR2 providing the strongest restriction in both TT as well as LL leprosy. These findings indicate that M. leprae hsps and their trypsin-digested fragments are promiscuous and recognizable in the context of diverse HLA alleles, of which DR2 is the most efficient restriction element. The 18-kDa fragment of hsp65 and the 3-kDa fragment of hsp18 are the most versatile fragments that could elicit in vitro proliferation in both polar forms of leprosy.

Original languageEnglish (US)
Pages (from-to)518-528
Number of pages11
JournalInternational Journal of Leprosy
Volume63
Issue number4
StatePublished - Dec 1 1995

ASJC Scopus subject areas

  • Dermatology

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