Determinants of T cell reactivity to the Mycobacterium leprae GroES homologue.
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.
Kim
J
J
Department of Microbiology and Immunology, University of California Los Angeles School of Medicine, 90095, USA.
Sette
A
A
Rodda
S
S
Southwood
S
S
Sieling
P A
PA
Mehra
V
V
Ohmen
J D
JD
Oliveros
J
J
Appella
E
E
Higashimoto
Y
Y
Rea
T H
TH
Bloom
B R
BR
Modlin
R L
RL
D000483:Alleles; D000595:Amino Acid Sequence; D000942:Antigens, Bacterial / Q000276:immunology; D018835:Chaperonin 10 / Q000235:genetics / Q000276:immunology*; D002999:Clone Cells; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D059847:HLA-DRB5 Chains; D006801:Humans; D008969:Molecular Sequence Data; D009166:Mycobacterium leprae / Q000276:immunology*; D017386:Sequence Homology, Amino Acid; D013601:T-Lymphocytes / Q000276:immunology*
D000942:Antigens, Bacterial; D018835:Chaperonin 10; D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059847:HLA-DRB5 Chains