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  • 1
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This article describes characterization of three new cross-reacting idiotopes, as recognized by mouse MoAbs, on human antibodies utilizing VH3 genes that are expressed in the early repertoire. Two of the mouse MoAbs (3H7 and 3H1) were raised against a human MoAb utilizing the DP47 (VH26) VH3 gene, whilst the third (7B4) was raised against a DP46 (GLSJ2) gene product. Evidence for the anti-idiotypic specificity of the mouse MoAbs was provided by their reactivity with the immunizing IgM, but not with Fcα, and by their specific inhibition of the binding between each immunizing antibody and its antigen. The three anti-idiotypic MoAbs were shown to be VH-specific reagents by the independence of their reactivity upon the L-chain type, or the untigenic specificity of the human MoAbs tested. Specificity of each mouse MoAb for VH3 gene-products was demonstrated by its sole cross-reactivity with VH3 proteins. Each anti-Id had a different reactivity pattern with a panel of MoAbs utilizing different VH3 genes. By relating the VH sequences of the tested VH3 proteins to their germline counterparts, 3H7 and 3H1 appeared to be specific for DP47-encoded proteins, although 3H1 had weak cross-reactivities with a few other VH3 gene-products. 7B4 appeared to be specific for antibodies utilizing DP46-related genes. Both 3H7 and 3H1 were also completely different to B6 and D12, two previously described MoAbs that also recognize VH3 proteins. Although 7B4 was similar to B6 and D12 in its binding to DP46-related gene products, B6 and D12 additionally recognized non DP46-related proteins and were thus different to 7B4.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: T lymphocytes have been implicated in the pathogenesis of rheumatoid arthritis. Interestingly, many of the activated T cells isolated from the synovial fluid of individuals with rheumatoid arthritis react with antigens from Mycobacterium tuberculosis or BCG. This response is seen to a much lesser extent in the peripheral blood of these patients. To investigate the nature of the T-cell response to BCG in RA, we isolated T cells from the synovial fluid of a patient with early-stage rheumatoid arthritis, stimulated them with BCG and cloned by limiting dilution. Staining with monoclonal antibodies specific for different Vβ gene families revealed a statistically significant greater proportion of synovial-derived T-cell clones expressing the Vβ8 gene family product compared with peripheral blood clones. While the antigen specificity of some of the clones could not be determined, several of the clones displayed distinct antigen reactivities. Sequencing the TCR P chain genes of these T cells suggested that although the Vβ8 gene products appeared to be over-represented in these BCG-specific clones, each clone utilized distinct Jβ gene segments and used N segment addition to different extents. In addition, no common motifs were identified in the β chain CDR3s of the clones sequenced. Analysis of bulk cultured BCG-specific SF T cells and unstimulated peripheral blood T cells for Vβ8 gene expression also revealed a large amount of diversity within the CDR3 region. Thus, the T-lymphocyte response to BCG in this patient with early rheumatoid arthritis appears to be quite heterogeneous.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: It has been recently established that retroviral envelope proteins (REPs) have structural features similar to those of immunoglobulins (Igs). In this study, we asked whether anti-REP antibodies cross-react with human Igs (hIgs). To this end, murine monoclonal antibodies (mMoAbs) that had been raised against a simian immunodeficiency virus (SIV) envelope protein, SIVMac251gp120, were screened for their ability to react with human monoclonal Igs (HMIgs). We show that two HMIgs, RFSJ2 (a rheumatoid factor) and PAMLN6 (a human anti-hIg V region antibody), but not a number of other HMIgs, could be weakly, but consistently, bound by anti-SIVMac251gp120 mMoAbs KK17 and KK46, as judged by indirect enzyme-linked immunosorbent assay and a liquid-phase inhibition immunoassay. Both mMoAbs are specific to amino acid residues in the V3 loop of the SIVMac251gp120. The RFSJ2 Ig heavy-chain V region (VH) is coded in part by a human VH gene, VH3–30.3 and includes the idiotope 7B4 (NKYY), which was previously shown to be present in the gp120 protein of a number of HIV-2 and SIV strains. However, an entirely different VH gene codes the PAMLN6 VH region, opening the possibility that epitope(s) shared between SIVMac251gp120 and hIgs may not be limited to the 7B4 idiotope.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Scandinavian journal of immunology 52 (2000), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: 7B4, B6 and D12 are murine monoclonal antibodies (MoAb) that bind to some human immunoglobulin heavy chain products of the closely related V3–30, V3–30.3 and V3–33 genes from the VH3 family. B6 and D12 have additional reactivities with some immunoglobulins (Ig) encoded by the V3–11 and V3–7 genes; D12 also reacts with some V3–43 gene Ig. We show here, by site-directed mutagensis, that the lysine at position 57 in the complementarity-determining region 2 (CDR-2) of the V3–30 gene product is crucial for epitope recognition by all three anti-VH3 MoAbs. Further analysis of the amino-acid sequences of a large panel of Ig reactive, or nonreactive, with MoAb 7B4 indicates that the determinant recognized by 7B4 is dependent on the presence of the tetrapeptide sequence NKYY between positions 56 and 59 in the CDR-2. Comparing the efficiency of 7B4 reactivity with VH3 gene-encoded human Ig indicates that amino-acid position 4 in the frame region 1 (FR-1) may also influence the binding of 7B4 to Ig encoded by three very closely related germline genes, V3–30, V3–30.3 and V3–33. NKYY is also found on the gp120 V3 region of human immunodeficiency virus (HIV)-2, SIV and HTLV-4. We also report that other tetrapeptide sequences found on the 56–59 motif of heavy chain variable regions encoded by germline genes are expressed on the solvent exposed V2 region of gp120 of HIV-1 isolates. The possible significance of these observations is discussed.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 435 (2005), S. 756-757 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] On 28 March 2005 the Sunda megathrust in Indonesia ruptured again, producing another great earthquake three months after the previous one. The rupture was contiguous with that of the December 2004 Sumatra–Andaman earthquake, and is likely to have been sparked by local stress, although the ...
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    [s.l.] : Nature Publishing Group
    Nature 434 (2005), S. 291-291 
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] Following the massive loss of life caused by the Sumatra–Andaman earthquake in Indonesia and its tsunami, the possibility of a triggered earthquake on the contiguous Sunda trench subduction zone is a real concern. We have calculated the distributions of co-seismic stress on this ...
    Type of Medium: Electronic Resource
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