Mycobacterium bovis BCG-induced human T-cell clones from BCG-vaccinated healthy subjects: antigen specificity and lymphokine production

Mustafa, Abu Salim; Kvalheim, Gunnar; Degré, Miklos; Godal, Tore

doi:10.1128/iai.53.3.491-497.1986

Cited by 30 publications

(21 citation statements)

References 15 publications

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“…paratubercuhsis in particular, in CD. The reported findings of raised anti-mycobacterial atitibody levels in sorne studies [18,22] tiiay merely represent previous exposure to other non-pathogenic species of mycobacteria which are ubiquitous in the environment, since it is clear, both from these data and other work, that mycobacterial species share common antigenic epitopes [34,35]. Indeed, in this study we have demonstrated a very high correlation between T cell proliferative responses towards the PPD preparations of Myco.…”

Section: Discussionsupporting

confidence: 47%

Peripheral cell-mediated immune response to mycobacterial antigens in inflammatory bowel disease

Rowbotham

Howdle

Trejdosiewicz

1995

Clinical and Experimental Immunology

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SUMMARYA mycobacterial etiology has been proposed In Crohn's disease (CD). We have sought evidence of increased or modified T lymphocyte immune responses to Mycnhactcrium tuberculosis and Myco. paratubercuhsis in patients with CD (ti = 13), compared with ulcerative colitis (UC; n = 17) and controls (« = 17). Peripheral blood cells were cultured with phytohaemagglutinin (positive mitogen control), mycobacterial purified protein derivative (PPD) preparations, lysates., column fractions and whole, heat-killed bacteria. Responses of T cells and T cell subsets were assessed by expression of activation markers (CD25. CD69). coupled with blast ogenesis assays (^H-thymidine uptake) and estimates of proliferation. Virtually all patients responded to Myco. paratuberculo.\is and Myco. tuberculosis antigens. There were no significant differences between patient groups, although there was a very high overall correlation (r = 095; P<0000\) between responses to the two mycobacterial species. Most of the activation and proliferative responses resided in the CD4'*' (T helper) subset. Although up to 15% of CDS"^ (suppressor/cytotoxic) cells also became activated, the CD8^ cells did not proliferate subsequently. Cells expressing the alternate y/) form of the T cell receptor (TCR 7(S^)did not activate or proliferate in response to mycobacterial antigens. There were no differences in any of these parameters between patient groups. We conclude that there is no specilic increase or alteration in cell-mediated anti-mycobacterial immunity in inflammatory bowel disease (IBD). Thus our data do not suppwrt a mycobacterial etiopathology of Crohn's disease.

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Section: Discussionsupporting

confidence: 47%

Peripheral cell-mediated immune response to mycobacterial antigens in inflammatory bowel disease

Rowbotham

Howdle

Trejdosiewicz

1995

Clinical and Experimental Immunology

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“…Furthermore, from peptide competition experiments we obtained the evidence that the difference between Dw4 and Dw14, in fact, may determine whether certain peptides will or will not bind to the given DR4 variant. The M. leprae 18 000 MW hsp epitope (aa [38][39][40][41][42][43][44][45][46][47][48][49][50] is an example of a peptide exclusively presented by Dw4 molecules, 38 whereas the M. leprae hsp 60 peptide (aa 343-355), as shown here, is only presented by Dw14 molecules. This M. leprae-specific epitope differs from the corresponding M. tuberculosis peptide by only one amino acid: threonine at position 349 in the M. leprae sequence is substituted by glutamine in the M. tuberculosis sequence (Fig.…”

Section: Discussionmentioning

confidence: 98%

“…The cultures were harvested, and the radioactivity incorporated was determined by standard methods. 45 The clones were considered responding to a given antigen or peptide when stimulation index was more than 5.…”

Section: Hla Typing Of Antigen-presenting Cellsmentioning

confidence: 99%

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

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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.

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“…The existence of a group of M. tuberculosis complex speci¢c antigens is also supported by results from crossreactivity studies with mycobacteria reactive monoclonal antibodies [16]. In contrast, several studies based on both T and B cell responses suggest that M. leprea is antigenically di¡erent from the M. tuberculosis complex [13,17,18]. In agreement with the above mentioned reports, our results support a close antigenic relationship between the species of the M. tuberculosis complex with regard to T cell determinants which have implications for diagnosis and vaccine design.…”

Section: Discussionmentioning

confidence: 97%

“…Results from other crossreactivity studies with mycobacteria reactive T cell clones indicate that the species of the M. tuberculosis complex are close antigenically related, as M. tuberculosis reactive clones frequently recognize M. africanum and M. bovis BCG but not other species [8,12^15]. Nevertheless, T cell clones speci¢c for M. tuberculosis and M. bovis BCG or M. tuber-culosis and M. africanum have also been reported [13,14]. The existence of a group of M. tuberculosis complex speci¢c antigens is also supported by results from crossreactivity studies with mycobacteria reactive monoclonal antibodies [16].…”

Section: Discussionmentioning

confidence: 99%

Mycobacterial crossreactivity of M. tuberculosis reactive T cell clones from naturally converted PPD positive healthy subjects

Oftung¹

1998

FEMS Immunology and Medical Microbiology

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Mycobacterium tuberculosis reactive CD4+, CD8- T cell clones were established from six naturally converted PPD positive healthy subjects by using whole bacilli as the primary stimulation antigen in vitro. Antigen specificity of the T cell clones was mapped by testing their proliferative response against a panel of pathogenic and environmental mycobacterial species. The crossreactivity patterns obtained showed that the T cell clones distributed along a spectrum from reactivity restricted to the M. tuberculosis complex to broadly crossreactive clones recognizing all mycobacterial species tested. Two of the T cell clones were able to discriminate between M. tuberculosis and M. bovis BCG, and importantly one of these clones was exclusively specific to M. tuberculosis. All of the CD4+ T cell clones tested, displayed MHC class II restricted cytotoxicity against macrophages pulsed with M. tuberculosis. In addition, some of these clones secreted GM-CSF upon antigen stimulation. The T cell clones described here represent relevant tools to identify and characterize target antigens of the immune response against M. tuberculosis with relevance to diagnosis and subunit vaccine design.

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Mycobacterium bovis BCG-induced human T-cell clones from BCG-vaccinated healthy subjects: antigen specificity and lymphokine production

Cited by 30 publications

References 15 publications

Peripheral cell-mediated immune response to mycobacterial antigens in inflammatory bowel disease

Peripheral cell-mediated immune response to mycobacterial antigens in inflammatory bowel disease

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

Mycobacterial crossreactivity of M. tuberculosis reactive T cell clones from naturally converted PPD positive healthy subjects

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