Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The beta chain of the T-cell antigen receptor present on 20 T-cell clones isolated from a tuberculoid leprosy patient was studied by gene rearrangement and PCR analysis. These T-cell clones all responded to Mycobacterium leprae-encoded protein antigens, and 8 of them specifically recognized peptides of the mycobacterial 65-kDa heat shock polypeptide (65hsp). All T-cell clones studied were HLA-DR-restricted (DR2 or -3). In the DR3-restricted group, 7 of 10 used a beta-chain variable region V beta 5 gene family member, whereas in the DR2-restricted group, 2 of 10 T-cell clones used a V beta 5 gene segment and 5 used the V beta 18 gene segment. The deduced amino acid sequences of the beta chain from 8 T-cell clones have revealed that 3 of 4 DR3-restricted T-cell clones expressed the V beta 5.1 gene segment whereas the fourth DR3-restricted T-cell clone employed a V beta 5 family member not previously described. The V beta 5.1-positive T-cell clones all recognized the same 65hsp peptide from residues 2 to 12. The N-D-N segment (where D is diversity) of the junctional region of these T-cell clones was very similar, despite different beta-chain joining gene segments. Of the 4 DR2-restricted T-cell clones investigated, 3 used the V beta 18 gene segment and recognized the 65hsp peptide from residues 418 to 427. In conclusion, within this panel of M. leprae-reactive T-cell clones, the DR3-restricted T-cell clones mainly used a V beta 5 gene segment, whereas the DR2-restricted clones employed preferentially the V beta 18 gene segment.
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PMID:T-cell receptor beta-chain gene usage in the T-cell recognition of Mycobacterium leprae antigens in one tuberculoid leprosy patient. 133 3

This study shows that normal human large granular lymphocytes (LGL) secrete tumor necrosis factor (TNF) in response to Mycobacterium avium-intracellulare complex (MAI). Percoll density gradient fractionation of peripheral mononuclear cells showed TNF activity in the fractions corresponding to LGL and not T cells, even when 5% monocytes were added to the T lymphocytes for accessory function. TNF release was not abrogated by treatment of the crude LGL preparations with anti-Leu M3, -CD4, and -CD8 antibodies (Ab) plus complement (C), but was abrogated by anti-CD16 and -CD2 Ab, as expected. Interestingly, anti-HLA-DR monoclonal antibody (mAb) treatment significantly diminished TNF activity from LGL, but maintained natural killer (NK) cell function unmodified as opposed to CD2+ and CD16+ cell depletion. Panning studies demonstrated that TNF secretion upon MAI stimulation resided only in the HLA-DR+ LGL and not the DR- LGL population. These results indicate that normal fresh HLA-DR+ LGL, as well as monocytes, are also responsible for rapid TNF secretion during early MAI infection. These DR+ cells appear to be distinct from those expressing NK function.
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PMID:Involvement of HLA-DR+ large granular lymphocytes in the induction of tumor necrosis factor by Mycobacterium avium-intracellulare complex. 168 7

Acquired cell-mediated immunity to intracellular parasites like mycobacteria is dependent on antigen-specific T lymphocytes. We have recently found that mycobacteria not only induce helper T cells but also cytotoxic CD4+ and/or CD8+ T cells as well as nonspecific killer cells that lyse human macrophages in vitro. In addition, we have described that the recombinant heat-shock protein (hsp) 65 of Mycobacterium bovis BCG/M, tuberculosis is an important target antigen for CD4+CD8- cytotoxic T cells. We have now further investigated the cytotoxic effector cells that are induced by the hsp65 of BCG. Purified protein derivative of tuberculin (PPD)- or hsp65-specific cytotoxic T cells specifically lysed PPD, hsp65 of BCG and hsp65 of M. leprae-pulsed macrophages in an HLA-DR-restricted manner. Nonpulsed macrophages were lysed to a much lower but still significant extent. hsp65-induced effector cells expressed CD3, CD5, CD4, CD8 and CD56 markers. Depletion experiments showed that the antigen-specific HLA-DR-restricted killer cell was of the CD5+CD4+CD8-CD56- phenotype. Experiments using N-terminal truncated hsp65 fusion (cro-lacZ) proteins suggested that the N-terminal 65 amino acid residues of the 540 amino acid molecule are critical for the expression of the cytotoxic target epitope(s) in two individuals tested. In addition to inducing antigen-specific cytotoxic effector cells, the hsp65 also triggered nonspecific nonrestricted effector cells with lytic activity against nonpulsed autologous or allogeneic macrophages as well as K-562 and Daudi tumor cells. hsp65-stimulated effector cells produced both interferon and tumor necrosis factor-alpha. An important finding was that hsp65-stimulated effector cells strongly inhibited colony-forming unit formation from live BCG-infected autologous macrophages.
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PMID:Induction of antigen-specific CD4+ HLA-DR-restricted cytotoxic T lymphocytes as well as nonspecific nonrestricted killer cells by the recombinant mycobacterial 65-kDa heat-shock protein. 169 Jan 36

Heat-killed whole Mycobacterium avium-Mycobacterium intracellulare complex (MAC) and its lipid component impaired the capacity of human peripheral blood mononuclear cells to proliferate in vitro in response to concanavalin A (ConA), purified protein derivative of tuberculin (PPD), and to a lesser degree, phytohemagglutinin stimulation. Inhibition by MAC was not contingent upon prior exposure of the donor to MAC or other mycobacteria and occurred with lymphocytes from tuberculin-negative as well as -positive subjects. The suppression was not due to the toxicity of MAC. The suppression by MAC was not blocked by indomethacin. Adherent cell depletion and cell mixing experiments with T cells indicated that monocytes and not T cells were a major contributor to the immunosuppression observed. However, neither interleukin-1 production nor the expression of HLA-DR (Ia antigen) by monocytes was suppressed by MAC treatment. On the other hand, treatment of monocytes with MAC or MAC-derived lipid resulted in significant decreases in CD11b, a member of the leukocyte function-associated molecule-1 and LeuM3 (CD14) molecule. Anti-CD18 (beta-chain of the leukocyte function-associated molecule-1 family) monoclonal antibody had suppressive effects on ConA- and PPD- but not phytohemagglutinin-induced in vitro lymphocyte blastogenesis. We suggest that MAC and MAC-derived lipid suppress the ConA- and PPD-induced T-cell proliferations by blocking the expression of accessory molecules on the surfaces of monocytes which might be involved in nonspecific monocyte-T-cell interactions and not by inhibiting either monocyte Ia antigen expression or interleukin-1 production by monocytes.
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PMID:Mycobacterium avium-Mycobacterium intracellular complex-induced suppression of T-cell proliferation in vitro by regulation of monocyte accessory cell activity. 169 Nov 44

We have been studying human T-cell clones that suppress anti-mycobacterial T-cell responses but not T-cell responses to an unrelated antigen or mitogen. In the present paper we report our studies on the activation requirements of these suppressor-T-cell clones. The suppressor-T-cell clones could proliferate and produce interferon-gamma upon stimulation with Mycobacterium leprae and other mycobacteria but not with unrelated antigens or autologous T cells. Both suppressor and nonsuppressor clones react to a 36-kDa antigen of M. leprae. Thus far, we have not been able to demonstrate whether they see the same or different epitopes. The antigen-driven proliferation of suppressor-T-cell clones was, however, significantly lower than that observed for T-cell clones that did not mediate suppression. The proliferation of suppressor-T-cell clones to M. leprae antigens could be blocked by monoclonal antibodies to HLA-DR, alpha beta T-cell receptor, interleukin-2 receptor, and, in the case of CD4-positive suppressor-T-cell clones, anti-CD4 monoclonal antibodies. DR restriction of the antigen presentation to these suppressor-T-cell clones was shown in mixing experiments using antigen-presenting cells as mononuclear cells from family members and unrelated individuals. These experiments also indicated that apart from regular DR-restriction a hitherto unknown factor may be required for presentation to or activation of suppressor-T-cell clones that is present in the family members and unrelated individuals with the same ethnic and geographic background but absent in DR/Dw-matched healthy Dutch individuals.
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PMID:Phenotypic and functional characterization of human suppressor T-cell clones: II. Activation by Mycobacterium leprae presented by HLA-DR molecules to alpha beta T-cell receptors. 169 23

The major histocompatibility complex (MHC) controls of the outcome of the immune response to T cell-dependent antigens by dictating whether T cell responsiveness will result (MHC-immune response [Ir]genes) or alternatively T cell nonresponsiveness will occur, possibly through the activation of suppressor cells (MHC-immune suppression [Is] genes). In mice, I-A molecules typically restrict antigen-specific helper T cells. In contrast, H-2 I-E molecules have been reported to control nonresponsiveness to a variety of antigens through antigen-specific suppressor cells. In analogy, HLA-DR molecules are the dominant restriction elements for helper T cells in man. This forces the question whether DQ molecules may be involved in controlling nonresponsiveness in man, e.g. through suppression. In one system, T cell nonresponsiveness to Schistosoma japonicum, evidence has been presented supporting this notion. We have now used a second system, Mycobacterium leprae-specific T cell nonresponsiveness, that is typically found in lepromatous leprosy patients. We find positive but limited evidence for a role for HLA-DQ molecules in controlling T cell nonresponsiveness to M. leprae of the 22 nonresponder patients tested, 4 showed a proliferative T cell response to M. leprae after the addition of DQ- but not DR-specific mAb to the cell cultures. In one of the four BCG nonresponders, anti-DQ mAb had a similar effect.
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PMID:HLA-DQ molecules and the control of Mycobacterium leprae-specific T cell nonresponsiveness in lepromatous leprosy patients. 170 Jul 54

The potential number of T-cell epitopes in the 19,000 molecular weight (MW) antigen has been investigated using overlapping peptides which comprise the complete sequence. Sixteen potential epitopes could be deduced from the responses to these peptides by polyclonal T cells derived from 22 antigen-responsive donors. The majority of epitopes were not predicted by either of the major paradigms, the Rothbard motif and the amphipathic helix. A hierarchy of epitopes was indicated by the responses, which ranged from strong and frequent in the N-terminal region, to moderate or weak elsewhere. Some epitopes were restricted by single HLA-DR determinants, or families of determinants sharing structural features in common, whilst the two N-terminal peptides were recognized by donors with a diversity of DR types. The high degree of T-cell recognition of the N-terminal region may be of relevance to the design of a sub-unit vaccine capable of priming T cells against Mycobacterium tuberculosis.
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PMID:Analysis of human T-cell epitopes in the 19,000 MW antigen of Mycobacterium tuberculosis: influence of HLA-DR. 171 49

Epidemiologic data indicates that blacks may be more susceptible than whites to infection by Mycobacterium tuberculosis. Resistance to the in vivo growth of Mycobacteria in mice correlates with the persistence of MHC class II expression by peritoneal macrophages. The expression of HLA-DR by human monocytes from different groups of individuals also differs. The increase in the expression of HLA-DR by monocytes that occurs upon in vitro culture was prevented by the protein synthesis inhibitor cycloheximide (CHX) in a majority of black donors. In contrast, the increase in HLA-DR expression by monocytes from the majority of white donors was unaffected.
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PMID:The expression of HLA-DR by monocytes from black and from white donors: different requirements for protein synthesis. 173 32

This study assesses the changes in the expression of histocompatibility antigen (HLA)-DR by mononuclear phagocytes from HIV-infected individuals. Overnight culture of monocytes resulted in an increase in HLA-DR expression by monocytes from uninfected individuals. In contrast, the expression of HLA-DR by monocytes from HIV-infected patients decreased spontaneously and was most pronounced in patients with clinical AIDS. We also found that Mycobacterium avium grew within monocytes from patients infected with HIV. The correlation between major histocompatibility complex (MHC) class II expression and Mycobacterial growth which has been reported in mice was not observed in monocytes from HIV-infected patients.
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PMID:Differences in the expression of histocompatibility antigen-DR and in anti-mycobacterial activity of monocytes from HIV-infected individuals. 176 81

Mechanisms of specific immunologic unresponsiveness or tolerance and their regulation by the major histocompatibility complex remain central issues in immunology. Recent findings that potentially reactive anti-self T cells are not completely clonally deleted in the thymus and that specific immunological unresponsiveness can be acquired in certain infectious diseases, such as leprosy, suggest that peripheral unresponsiveness can be developed and maintained in adults. Human antigen-specific T suppressor cells represent one mechanism of peripheral tolerance. Clones of CD8+ T suppressor cells have been derived from blood or lesions of patients with lepromatous leprosy who are selectively unable to mount cellular immunity to Mycobacterium leprae. Using a panel of M. leprae-specific CD4+ and CD8+ T-cell clones of differing major histocompatibility complex class II haplotypes, suppression in vitro was found to be restricted by HLA-DQ and not by HLA-DR and inhibited by antibodies to HLA-DQ. In addition, antigen-induced suppression could be inhibited by antibodies specific to appropriate polymorphic T-cell receptor beta chains of the CD8+ clones. The results establish that activation of specific T suppressor cells is dependent on their polymorphic T-cell receptors and suggest that HLA-DQ serves as the preferred restricting element for suppression.
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PMID:Immunological suppression by human CD8+ T cells is receptor dependent and HLA-DQ restricted. 182 57


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