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  • 1
    Electronic Resource
    Electronic Resource
    Molecular mimicry in diabetes mellitus: the homologous domain in coxsackie B virus protein 2C and islet autoantigen GAD65 is highly conserved in the coxsackie B-like enteroviruses and binds to the diabetes associated HLA-DR3 molecule (1998)
    Springer
    Diabetologia 41 (1998), S. 40-46 
    Details
    ISSN: 1432-0428
    Keywords: Keywords Coxsackie B virus ; peptide binding ; HLA-DR ; molecular mimicry ; IDDM.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary It has been proposed that molecular mimicry between protein 2C (p2C) of coxsackie virus B4 and the autoantigen glutamic acid decarboxylase (GAD65) plays a role in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). In this study we show that the amino acid sequence of p2C which shares homology with a sequence in GAD65 (PEVKEK), is highly conserved in coxsackie virus B4 isolates as well as in different viruses of the subgroup of coxsackie B-like enteroviruses. These are the most prevalent enteroviruses and therefore exposure to the mimicry motif will be a frequent event throughout life. Presentation of the homologous peptides by HLA molecules is essential for T-cell reactivity. Therefore, we tested whether the PEVKEK motif can bind to the IDDM-associated HLA-DR1, -DR3 and -DR4 molecules. Synthetic peptides with sequences derived from p2C and GAD65 did bind to HLA-DR3 but not to HLA-DR1 or -DR4. Replacement of amino acids within the motif showed that the PEVKEK motif binds specifically to HLA-DR3. Moreover, both p2C and GAD65 peptides bind in the same position within the peptide binding groove of the DR3 molecule which is an essential requirement for T-cell cross-reactivity. The results support molecular mimicry between p2C of coxsackie B-like enteroviruses and GAD65. However, this molecular mimicry may be limited to the HLA-DR3 positive subpopulation of IDDM patients. [Diabetologia (1998) 41: 40–46]
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s001250050864
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  • 2
    Electronic Resource
    Electronic Resource
    HLA Class-II-restricted Mycobacterium lepraereactive T-Cell Clones from Leprosy Patients Established with a Minimal Requirement for Autologous Mononuclear Cells (1986)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 23 (1986), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This report describes an effective method for the cloning of Mycobacterium leprae reactive T lymphocytes with Epstein-Barr-virus transformed autologous B cells as antigen-presenting cells- The two advantages of this method are that it drastically reduces the number of autologous peripheral blood mononuclear cells I (〈107 cells) needed to obtain and propagate these T-cell clones (TLC). and that it enables us to expand individual TLC to large numbers of cells (〈108) Thus she major obstacles for the cloning of T lymphocytes-especially important with regard to patients-are bypassed. Thus far. TLC Srom three leprosy patients have been established. These TLC are HLA class H restricted in their M. leprae directed response. A marked enhancement in antigen responsiveness was observed after further expansion of several TLC. some of which turned from nonresponder into responder TLC, Four tested TLC display strikingly different antigen recognition patterns when tested against a number of other mycobacterial antigens: one T.LC so far recognizes only M leprae antigens.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1986.tb01947.x
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  • 3
    Electronic Resource
    Electronic Resource
    Immunological Crossreactivity of the Mycobacterium leprae CFP-10 with its Homologue in Mycobacterium tuberculosis (2004)
    Oxford, UK; Malden , USA : Blackwell Science Ltd
    Scandinavian journal of immunology 59 (2004), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Mycobacterium tuberculosis culture filtrate protein-10 (CFP-10) (Rv3874) is considered a promising antigen for the immunodiagnosis of tuberculosis (TB) together with early secreted antigens of M. tuberculosis (ESAT-6). Both ESAT-6 and CFP-10 are encoded by the RD1 region that is deleted from all tested M. bovis bacille Calmette–Guérin (BCG) strains but present in M. leprae, M. tuberculosis, M. bovis, M. kansasii, M. africanum and M. marinum. In this study, the homologue of CFP-10 in M. leprae (ML0050) is identified and characterized. Interferon-γ production in response to this homologue by T cells from leprosy patients, TB patients and unexposed controls shows that CFP-10 of M. leprae is a potent antigen that crossreacts with CFP-10 of M. tuberculosis at the T-cell level. This crossreactivity has implications for the use of CFP-10 of these mycobacterial species as diagnostic tool in areas endemic for both the diseases.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.0300-9475.2004.01358.x
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  • 4
    Electronic Resource
    Electronic Resource
    Intradermal Recombinant Interleukin 2 Enhances Peripheral Blood T-Cell Responses to Mitogen and Antigens in Patients with Lepromatous Leprosy (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 32 (1990), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Thirty-one patients with lepromatous leprosy received recombinant interleukin 2 (IL-2) intradermally in doses ranging from 10 to 30 μg. Before injection and at time intervals of 2–21 days thereafter, samples of peripheral blood mononuclear cells (PBMC) were obtained. Single or multiple injections (1–3) of IL-2 did not modify the total number of circulating lymphocytes or the number of T cells and the CD4/CD8 T-cell ratio However. IL-2 had a pronounced influence on the [3H]thymidine incorporation in response to various stimuli 4–8 days alter intradermal IL-2. Stimulation indices of three- to sevenfold above pre-IL-2 levels were observed with the polyclonal activator phytohaemagglutinin (PHA) and enhanced thymidine incorporation occurred in the presence of antigens to which the patients were already sensitized, such as purified protein derivative and BCG. IL-2 had no effect on the unresponsive stale of lepromatous leprosy patient T cells to the antigens of Mycobacterium leprae.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1990.tb02897.x
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  • 5
    Electronic Resource
    Electronic Resource
    A Comparative Study on the Effects of rIL-4, rIL-2, rIFN-γ, and rTNF-α on Specific T-Cell Non-Responsiveness to Mycobacterial Antigens in Lepromatous Leprosy Patients in Vitro (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 31 (1990), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have studied lepromatous leprosy (LL) as a human model disease for T-cell non-responsiveness to specific mycobacterial antigens and studied the effect of rlL-4, rIL-2, rlFN-y and rTNF-x thereon. T-cell non-responsiveness to Mycobacierium bovis bacillus Calmette-Guerin (BCG) or purified protein derivative of M. tuberculosis (PPD) antigens could be overcome in 5 out of 8 non-responder patients by rlL-2 and in 2 out of 8 by rlL-4. The ability of rIL-4 to overcome BCG/PPD non-responsiveness was strongly dose-dependent. When rIL-2 and rIL-4 were added simultaneously, they seemed to synergize in their effect. T-cell non-responsiveness to M. leprae could be overcome only in 2 out of 18 non-responders by rIL-2 but not by rIL-4 alone. The ability of rlL-2 to overcome T-cell non-responsiveness to M. leprae antigens became particularly marked when the recombinant 65-kDa heat shock antigen of M. leprae was used instead of whole bacilli. Exogenously added rIL-4, and to a lesser extent rlL-2, strongly enhanced existing T-cell responses to BCG or M. leprae in the majority (8 out of 11) of responders. These findings may have implications for the in vivo manipulation of the immune response by recombinant lymphokines and vaccines.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1990.tb02806.x
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  • 6
    Electronic Resource
    Electronic Resource
    Epstein-Barr Virus-Transformed B Cell Lines Present M. Leprae Antigens to T Cells (1985)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 22 (1985), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have investigated whether or not Epstein-Barr virus-transformed lymphoblastoid B cell lines (EBV-BLCL) are able to present Mycobacterium leprae (M. leprae) to antigen-reactive T cell lines and clones. Such EBV-BLCL would provide us with a homogeneous and unlimited source of antigen-presenting cells. Antigen-triggered proliferation of T cells has been studied with co-cultures either with autologous or allogeneic irradiated EBV-BLCL. Our results show that EBV-BLCL are able to present M. leprae as efficiently as peripheral blood mononuclear cells, and that they also function in an HLA-DR-restricted fashion. Apart from their possible in vivo relevance, these results have important practical implications, in particular for the generation and study of M. leprae-reactive T-cell clones.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1985.tb01918.x
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  • 7
    Electronic Resource
    Electronic Resource
    Cellular, Humoral, and Gamma Interferon Responses to Mycobacterium leprae and BCG Antigens in Healthy Individuals Exposed to Leprosy (1988)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 27 (1988), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Protective immunity against mycobacteria is dependent on antigen-specific T cells. The antibodies induced upon immunization with mycobacteria have no apparent role in host protection. Serological techniques have detected some antigens that are also recognized by human T cells but may fail to recognize others. Potentially, there may he differences in the epitopes seen by the T and B cell anti-mycobacterial antigen repertoires- We have screened the different components of sonicated BCG or Mycobacterium leprae that were separated according to their molecular weight (MW) by SDS-PAGEI and then electroblotted on nitrocellulose paper. The blots were cut into squares and tested directly in a T cell proliferation assay. Our results indicate that peripheral T cells of healthy leprosy patient contacts respond preferentially to the tower MW (〈70,000) and not the higher MW fractions of M. leprae and BCG, in contrast to the humoral response of these same individuals. The most important fractions in inducing a lymphoproliferative response were in the regions of 11–16kDa of BCG and M. leprae and to the 22–26kDa region of M. leprae. These fractions appeared to represent molecular weight regions that were in some instances clearly distinct from previously defined antigens. It was further shown that lymphoproliferation in response to mycobacterial fractions correlated with the production of gamma interferon, a lymphokine required for macrophage activation and elimination of mycobacteria. These studies allow the direct assessment of antigens involved in protective T cell-mediated immunity, and should be helpful in selecting relevant antigens for skin testing and immunization.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1988.tb02378.x
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  • 8
    Electronic Resource
    Electronic Resource
    HLA Class II+ Human Keratinocytes present Mycobacterium leprae Antigens to CD4+ Thl-Like Cells (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 37 (1993), S. 0 
    Details
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In a variety of inflammatory skin diseases like leprosy, keratinocytes (KC) are induced to express MHC class II molecules and may therefore serve as antigen-presenting cells (APC) for MHC class II restricted T cells infiltrating the lesions. However, KC have been thought to be improper APC for MHC class II restricted T cells and to drive T cells into an anergic rather than into an activation state. We evaluated this issue in relation to leprosy and tested whether HLA-DR+ KC could present M. leprae antigens to well-defined, CD4 +, cytotoxic as well as proliferative, Thl -like cell clones. Using a recently developed sensitive assay system which employs intact layers of basal KC as APC we found that most T-cell clones (6/8) lysed HLA-DR+ KC pulsed with M. leprae antigens. KC were only recognized after induction of HLA-DR expression by IFN-γ, in an antigen-specific and HLA class II restricted manner. All T-cell clones tested also showed significant proliferation and IFN-γ production in response to M. leprae antigens presented by HLA-DR+ KC, arguing against a KC dependent anergizing effect on T cells. Thus, HLA class II+ KC can function as proper APC for HLA class II restricted CD4+ Th l -like cells. It seems therefore possible that antigen presentation by KC contributes to the local cell-mediated immune responses in DTH lesions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-3083.1993.tb01663.x
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  • 9
    Electronic Resource
    Electronic Resource
    Molecular and immunological analysis of a fibronectin-binding protein antigen secreted by Mycobacterium leprae (1992)
    Oxford, UK : Blackwell Publishing Ltd
    Molecular microbiology 6 (1992), S. 0 
    Details
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: By screening a Mycobacterium lepraeλgt11 genomic DNA library with leprosy-patient sera we have previously identified 50 recombinant clones that expressed novel M. leprae antigens (Sathish et al., 1990). In this study, we show by DNA sequencing and immunoblot analysis that three of these clones express a M. leprae homologue of the fibronectin-binding antigen 85 complex of mycobacteria. The complete gene was characterized and it encodes a 327-amino-acid polypeptide, consisting of a consensus signal sequence of 38 amino acids followed by a mature protein of 289 amino acids. This is the first sequence of a member of the M. leprae antigen 85 complex, and Southern blotting analysis indicated the presence of multiple genes of the 85 complex in the genome of M. leprae. The amino acid sequence displays 75–85% sequence identity with components of the antigen 85 complex from M. tuberculosis, M. bovis BCG and M. kansasii. Furthermore, antibodies to the antigen 85 complex of M. tuberculosis and M. bovis BCG reacted with two fusion proteins containing the amino acid regions 55–266 and 265–327 of the M. leprae protein. The M. leprae 30/31 kDa protein induces strong humoral and cellular responses, as judged by Western blot analysis with patient sera and proliferation of T cells derived from healthy individuals and leprosy patients. Amino acid regions 55–266 and 265–327 both were shown to bind to fibronectin, indicating the presence of at least two fibronectin-binding sites on the M. leprae protein. These data indicate that this 30/31 kDa protein is not only important in the immune response against M. leprae, but may also have a biological role in the interaction of this bacillus with the human host.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1365-2958.1992.tb01996.x
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