Cross-reactive epitopes and HLA-restriction elements in human T cell recognition of the Mycobacterium leprae 18-kD heat shock protein.
We have previously demonstrated that the Mycobacterium leprae 18-kD heat shock protein (HSP18) is represented among the antigenic targets of human T cell responses induced by M. leprae immunization and that the peptide 38-50 serves as an immunodominant epitope recognized by CD4+ T cell clones. By using peripheral blood mononuclear cells and T cell lines from the same donor group, we have in this study shown that the M. leprae HSP18 and peptide 38-50 were recognized by memory T cells 8 years after immunization with M. leprae. The finding that M. bovis BCG-induced T cell lines responded to M. leprae HSP18, but not to the peptide 38-50, suggested the existence of additional T cell epitopes of a cross-reactive nature. Consistent with this, testing of the T cell lines for proliferative responses to the complete HSP18 molecule, truncated HSP18 (amino acid (aa) residues 38-148) and overlapping synthetic peptides, made it possible to identify two cross-reactive epitope regions defined by aa residues 1-38 and 41-55. While peptide 38-50-reactive T cell clones showed limited cross-reactivity by responding to M. leprae, M. avium and M. scrofulaceum, the T cell lines specific to the epitopes 1-38 and 41-55 were broadly cross-reactive, as demonstrated by their response to M. leprae, M. tuberculosis complex, M. avium and other mycobacteria. MHC restriction analysis of the HSP18-responding T cell lines showed that the epitopes 1-38 and 38-50 were presented by one of the two HLA-DR molecules expressed from self HLA-DRB1 genes, whereas the epitope 41-55 was recognized in the presence of autologous as well as HLA-DR and HLA-DQ mismatched allogeneic antigen-presenting cells. The results obtained in this study made it possible to identify cross-reactive T cell epitopes of the M. leprae HSP18, and provide an explanation for T cell recognition of this antigen in individuals infected with species of the M. tuberculosis complex or environmental mycobacteria.
Mustafa
A S
AS
Department of Microbiology, Faculty of Medicine, Kuwait University, Safat, Kuwait. abusalim@hsc.kuniv.edu.kw
Lundin
K E
KE
Meloen
R H
RH
Oftung
F
F
D000595:Amino Acid Sequence; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D000942:Antigens, Bacterial; D001426:Bacterial Proteins / Q000737:chemistry / Q000276:immunology; D018984:Epitopes, T-Lymphocyte / Q000032:analysis / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D006360:Heat-Shock Proteins / Q000737:chemistry / Q000276:immunology*; D006650:Histocompatibility Testing; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D009163:Mycobacterium bovis / Q000276:immunology; D009166:Mycobacterium leprae / Q000276:immunology*; D010455:Peptides / Q000032:analysis / Q000276:immunology; D013045:Species Specificity; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D018984:Epitopes, T-Lymphocyte; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D006360:Heat-Shock Proteins; D010455:Peptides; C081475:hsp18 protein, bacteria