1,721,116 research outputs found
Interaction of anti-idiotype antibodies with the surface of neoplastic lymphocytes
No full textA panel of monoclonal anti-idiotype antibodies specific for cell surface immunoglobulin (Ig) of the L2C leukaemia of guinea pigs has been investigated. Equilibrium constants were established for reaction of the antibodies with surface Ig in situ. They ranged between 108 and 109M-1 for intact IgG antibodies, and 10' and 108M-1 for their Fab'γ fragments. Values at O^u and 37^u were similar. All antibodies were shown to bind bivalently at equilibrium but showed striking differences in their ability to clear Ig from the L_2C cell surface by antigenic modulation in vitro. Differences in the ability to induce antigenic modulation correlated with the readiness of different antibodies to cross-link neighbouring Ig molecules and evidence is presented for the existence of two distinct types of anti-idiotype antibody: 1) those which form intra-Ig bridges and do not favour modulation (monogamous binders), 2) those which form inter-Ig bridges and favour modulation (bigamous binders). Competitive binding assays showed that simultaneous access of more than one anti-idiotype antibody is generally not permitted. This approach therefore revealed no gross spatial separation of the target determinants of monogamously and bigamously binding antibodies. Fab' arms from two monoclonal antibodies have been used in the preparation of univalent antibodies (FabFc and FabIgG) where Fab' is joined to xenogeneic effector (IgG or Fc) via tandem thioether bonds. The effector capabilities (complement cytotoxicity and antibody dependent cellular cytotoxicity) of a number of chimeric univalent antibodies sharing the same monoclonal Fab' arm but with various effector moieties were investigated and shown to differ according to the species donating the Fc or IgG moiety. In general, those univalent antibodies which were efficient recruiters of effectors in vitro gave the best protection against L_2C leukaemia in therapeutic trials, though by 1) using univalent antibodies which were poor activators of complement and 2) running trials in congenitally C3 deficient guinea pigs, the role of complement in tumour combat would seem to be relatively unimportant. By preparing univalent antibodies which share the same effector region by carry Fab's of different affinity, the role of affinity in therapeutic efficacy was shown to be minimal, although the available range of affinities was narrow. (D72232/87)</p
The role of MHC I protein dynamics in tapasin and TAPBPR-assisted immunopeptidome editing
No full textMajor Histocompatibility Complex class I (MHC I) molecules are highly polymorphic, with allotypes differing in peptide binding preferences, and in their dependence upon tapasin for optimal peptide selection. The tapasin dependence of MHC allotypes is inversely correlated with their self-editing ability, and underpinned by conformational plasticity. Recently, TAPBPR has been shown to enhance MHC I assembly via a chaperone-like function, and by editing the peptide repertoire of some MHC I allotypes. Structural analysis has shown TAPBPR binding changes the conformation and dynamics of MHC I, with MHC protein dynamics likely to determine the prevailing TAPBPR function: generically enhancing MHC I assembly by stabilising highly dynamic peptide-empty MHC I; and by editing the peptide repertoire of highly dynamic MHC I allotypes
Recent advances in Major Histocompatibility Complex (MHC) class I antigen presentation: Plastic MHC molecules and TAPBPR-mediated quality control [version 1; referees: 4 approved]
No full textWe have known since the late 1980s that the function of classical major histocompatibility complex (MHC) class I molecules is to bind peptides and display them at the cell surface to cytotoxic T cells. Recognition by these sentinels of the immune system can lead to the destruction of the presenting cell, thus protecting the host from pathogens and cancer. Classical MHC class I molecules (MHC I hereafter) are co-dominantly expressed, polygenic, and exceptionally polymorphic and have significant sequence diversity. Thus, in most species, there are many different MHC I allotypes expressed, each with different peptide-binding specificity, which can have a dramatic effect on disease outcome. Although MHC allotypes vary in their primary sequence, they share common tertiary and quaternary structures. Here, we review the evidence that, despite this commonality, polymorphic amino acid differences between allotypes alter the ability of MHC I molecules to change shape (that is, their conformational plasticity). We discuss how the peptide loading co-factor tapasin might modify this plasticity to augment peptide loading. Lastly, we consider recent findings concerning the functions of the non-classical MHC I molecule HLA-E as well as the tapasin-related protein TAPBPR (transporter associated with antigen presentation binding protein-related), which has been shown to act as a second quality-control stage in MHC I antigen presentation
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
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