02642nas a2200445   4500000000100000008004100001260001300042653002700055653002400082653002300106653003100129653001800160653001600178653002400194653003100218653002000249653001100269653001200280653002500292653002500317653002600342653002500368653002200393653002500415653001200440100001400452700001400466700001400480700001500494700001300509700001700522700001400539700002100553245015200574856004100726300001100767490000700778520139700785022001402182       1995                            d  c1995 Dec10aAntibodies, Monoclonal10aAntigens, Bacterial10aBacterial Proteins10aCD4-Positive T-Lymphocytes10aChaperonin 6010aChaperonins10aHeat-Shock Proteins10aHistocompatibility Testing10aHLA-DR Antigens10aHumans10aleprosy10aLeprosy, lepromatous10aLeprosy, Tuberculoid10aLymphocyte Activation10aMycobacterium leprae10aPeptide Fragments10aRecombinant Proteins10aTrypsin1 aMitra D K1 aMehra N K1 aMaiti T K1 aBanerjee A1 aTaneja V1 aRajalingam R1 aAhuja R K1 aBhattacharya B C00aCD4+ T-cell responses to recombinant hsp65 and hsp18 of M. leprae and their trypsin-digested fragments in leprosy: diversity in HLA-DR restriction.  uhttp://ila.ilsl.br/pdfs/v63n4a02.pdf  a518-280 v633 a<p>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 &gt; 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.</p>
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