Human T cells recognize mycobacterial heat shock proteins in the context of multiple HLA-DR molecules: studies with healthy subjects vaccinated with Mycobacterium bovis BCG and Mycobacterium leprae

Mustafa, Abu Salim; Lundin, Knut E.A.; Oftung, Fredrik

doi:10.1128/iai.61.12.5294-5301.1993

Cited by 66 publications

(38 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HLA restriction analysis showed that all of these T cell clones recognized HSP70 in the context of HLA-DR3 molecules. This observation is consistent with our earlier report that HLA-DR3 is used as a restriction element in antigen-induced proliferation of HSP70 reactive human T cell lines [30]. In addition, we have also identi¢ed one HLA-DR3 restricted T cell epitope recognized by T cell clones from tuberculoid leprosy patients, but cross-reactivity studies showed that these clones were M. leprae and not M. tuberculosis speci¢c [14,26].…”

Section: Discussionsupporting

confidence: 91%

Identification of mycobacterial HSP70 reactive human T cell clones discriminating between M. tuberculosis and M. leprae

Oftung¹

1998

FEMS Immunology and Medical Microbiology

Self Cite

View full text Add to dashboard Cite

M. tuberculosis reactive CD4+ T cell clones were established from a BCG vaccinated donor and tested for proliferative responses against complex mycobacterial antigens like M. tuberculosis, M. leprae, and PPD, as well as the recombinant M. tuberculosis HSP70 and HSP65 antigens from both M. tuberculosis and M. leprae. This screening permitted the identification of T cell clones specifically recognizing the mycobacterial HSP70 or HSP65 antigen. All HSP65 reactive T cell clones were cross-reactive for M. tuberculosis and M. leprae, whereas three HSP70 reactive T cell clones only recognized M. tuberculosis. In addition, HLA typing and blocking experiments with anti-HLA antibodies revealed that antigen presentation to all M. tuberculosis reactive T cell clones was restricted by HLA-DR3 molecules. We have thereby demonstrated the presence of human T cell specificities directed against the mycobacterial HSP70 antigen that are able to discriminate between M. tuberculosis and M. leprae.

show abstract

Section: Discussionsupporting

confidence: 91%

Identification of mycobacterial HSP70 reactive human T cell clones discriminating between M. tuberculosis and M. leprae

Oftung¹

1998

FEMS Immunology and Medical Microbiology

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, two T cell epitopes cross-reactive between M. leprae, the M. tuberculosis complex and environmental mycobacteria were identified. One of these epitopes was presented to T cells by autologous as well as HLA-DR-and DQ-mismatched allogeneic APC, which confirmed our previous observation that the complete M. leprae HSP18 molecule could be recognized in association with multiple HLA-DR molecules [10]. The presence of T cell epitopes recognized as cross-reactive for pathogenic as well as environmental mycobacterial species suggests that the M. leprae HSP18 antigen should not be used for diagnosis.…”

Section: Discussionsupporting

confidence: 84%

Cross-reactive epitopes and HLA-restriction elements in human T cell recognition of theMycobacterium leprae18-kD heat shock protein

Mustafa

Lundin²,

Meloen³

et al. 2000

Clinical and Experimental Immunology

Self Cite

View full text Add to dashboard Cite

SUMMARYWe 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 1 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.

show abstract

“…We recently demonstrated recognition of the M. leprae hsp 60 by polyclonal T-cell lines in the context of HLA-DR4 from three HLA-DR4-positive subjects previously immunized with Mycobacterium bovis bacillus Calmette-Guérin (BCG) and M. leprae. 3 One of these individuals was HLA-DR4 homozygous and the other two were heterozygous for HLA-DR4. In order to map these T-cell epitopes recognized at the amino acid sequence level, we have raised and tested M. leprae hsp 60-reactive T-cell clones from these donors against synthetic peptides.…”

Section: Leprae Hsp 60-reactive T-cell Clonesmentioning

confidence: 98%

“…Cellular immune responses to the mycobacterial hsp 60 have been demonstrated by proliferation as well as cytotoxicity assays. [1][2][3][4][5][6][7] The cytokines produced by Th1 cells [interleukin-2 (IL-2), interferon-g (IFN-g) and granulocyte-macrophage colony-stimulating factor (GM-CSF)], which mediate protective immunity to mycobacteria, have been shown to be released from hsp 60reactive T-cell clones. 8,9 Immunization of experimental animals with hsp 60 or hsp 60 reactive T cells protects against challenge with viable M. tuberculosis, 10,11 M. leprae 12 and other bacterial pathogens.…”

Section: Introductionmentioning

confidence: 99%

“…13,14 At the molecular level, a large number of epitopes recognized by hsp 60 reactive T-cell clones have been defined mainly by the use of synthetic peptides, 9,[15][16][17][18] and major histocompatibility complex (MHC) restriction analysis has demonstrated that these epitopes are recognized by T cells in the context of several HLA-DR molecules. 3,18,19 These results have made the mycobacterial hsp 60 a potential candidate in subunit vaccine design against mycobacterial diseases.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

HLA‐DR4‐restricted T‐cell epitopes from the mycobacterial 60 000 MW heat shock protein (hsp 60) do not map to the sequence homology regions with the human hsp 60

Mustafa

Lundin²,

Meloen

et al. 1996

Immunology

View full text Add to dashboard Cite

SUMMARYThe mycobacterial 60 000 MW heat shock protein (hsp 60) is a major antigen recognized by mycobacteria-reactive human CD4T cells with lymphokine profiles and effector functions consistent with protective immunity. In addition, the presence of a large number of T-cell epitopes presented by several HLA class II molecules makes this antigen relevant to subunit vaccine design. However, the results from animal models as well as human studies suggest that the mycobacterial hsp 60 may induce T-cell-mediated autoimmune conditions. In humans, the expression of HLA-DR4 represents a risk factor for some autoimmune diseases. These observations suggest that the epitopes from the mycobacterial hsp 60 presented to T cells in the context of HLA-DR4 could be relevant to autoimmunity. This is the first report on identification of HLA-DR4-restricted T-cell epitopes from the mycobacterial antigen hsp 60. In total, five epitopes recognized in the context of HLA-DR4 by the M. leprae hsp 60-reactive CD4 T-cell clones from a subject immunized with M. leprae were defined by synthetic peptides. Two of the epitopes were M. leprae-specific (aa 343-355, aa 522-534), whereas three epitopes were common to M. leprae and M. tuberculosis (aa 331-345, aa 441-455, aa 501-515). However, all of these epitopes belong to the regions that are highly divergent between the mycobacterial hsp 60 and the homologous human hsp 60 sequence, suggesting that the T cells recognizing the mycobacterial hsp 60 in the context of HLA-DR4 may not necessarily induce autoreactivity.

show abstract

Human T cells recognize mycobacterial heat shock proteins in the context of multiple HLA-DR molecules: studies with healthy subjects vaccinated with Mycobacterium bovis BCG and Mycobacterium leprae

Cited by 66 publications

References 39 publications

Identification of mycobacterial HSP70 reactive human T cell clones discriminating between M. tuberculosis and M. leprae

Identification of mycobacterial HSP70 reactive human T cell clones discriminating between M. tuberculosis and M. leprae

Cross-reactive epitopes and HLA-restriction elements in human T cell recognition of theMycobacterium leprae18-kD heat shock protein

HLA‐DR4‐restricted T‐cell epitopes from the mycobacterial 60 000 MW heat shock protein (hsp 60) do not map to the sequence homology regions with the human hsp 60

Contact Info

Product

Resources

About