02125nas a2200433 4500000000100000008004100001260001600042653001200058653002400070653002400094653001800118653001600136653002700152653002000179653002000199653001100219653002800230653002500258653003400283653001800317100001000335700001200345700001200357700001600369700001600385700001200401700001400413700001500427700001400442700001800456700001200474700001400486700001500500245008300515300001100598490000800609520106000617022001401677 1997 d c1997 Jul 0110aAlleles10aAmino Acid Sequence10aAntigens, Bacterial10aChaperonin 1010aClone Cells10aEpitopes, T-Lymphocyte10aHLA-DR Antigens10aHLA-DRB5 Chains10aHumans10aMolecular Sequence Data10aMycobacterium leprae10aSequence Homology, Amino Acid10aT-Lymphocytes1 aKim J1 aSette A1 aRodda S1 aSouthwood S1 aSieling P A1 aMehra V1 aOhmen J D1 aOliveros J1 aAppella E1 aHigashimoto Y1 aRea T H1 aBloom B R1 aModlin R L00aDeterminants of T cell reactivity to the Mycobacterium leprae GroES homologue. a335-430 v1593 a

The 10-kDa protein Ag of Mycobacterium leprae, a human GroES hsp10 cognate, is a major T cell Ag in human leprosy infection. We investigated the mechanism for T cell responsiveness to this Ag according to the trimolecular interaction between T cell, peptide, and Ag-presenting element. This research was accomplished by mapping T cell epitopes in leprosy patients and correlating these responses with peptide-MHC binding affinities. We found that the majority of tuberculoid leprosy patients responded to peptides corresponding to residues 25-39 and 28-42. Truncation analysis of these peptides mapped the exact epitope to be within the overlapping region comprising residues 28-39. Responsiveness was correlated with the HLA-DRB5*0101 allele, which bound the peptides with moderate affinity. This allele is linked to HLA-DR2, which is associated with the resistant form of leprosy. Therefore, T cell responsiveness in tuberculoid leprosy may be mediated by the ability of HLA-DRB5*0101 to bind and present peptides of the immunodominant 10-kDa Ag.

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