1,720,957 research outputs found
Molecular requirements for T cell recognition by a major histocompatibility complex class II-restricted T cell receptor: The involvement of the fourth hypervariable loop of the Vα domain
No full textThe role of two central residues (K68, E69) of the fourth hypervariable loop of the Vα domain (HV4α) in antigen recognition by an MHC class II- restricted T cell receptor (TCR) has been analyzed. The TCR recognizes the NH2-terminal peptide of myelin basic protein (Ac1-11, acetylated at NH2 terminus) associated with the class II MHC molecule I-A(u). Lysine 68 (K68) and glutamic acid 69 (E69) of HV4α have been mutated both individually and simultaneously to alanine (K68A, E69A). The responsiveness of transfectants bearing wild-type and mutated TCRs to Ac1-11-I-A(u) complexes has been analyzed in the presence and absence of expression of the coreceptor CD4. The data demonstrate that in the absence of CD4 expression, K68 plays a central role in antigen responsiveness. In contrast, the effect of mutating E69 to alanine is less marked. CD4 coexpression can partially compensate for the loss of activity of the K68A mutant transfectants, resulting in responses that, relative to those of the wild-type transfectants, are highly sensitive to anti-CD4 antibody blockade. The observations support models oft cell activation in which both the affinity of the TCR for cognate ligand and the involvement of coreceptors determine the outcome of the T cell-antigen- presenting cell interaction.</p
Characterization of the interaction of a TCR α chain variable domain with MHC II I-A molecules
No full textThe αβ TCR recognizes peptides bound to MHC molecules. In the present study, we analyzed the interaction of a soluble TCR α chain variable domain (V(α)4.2-J(α)40; abbreviated to V(α)4.2) with the MHC class II molecule I-A(u). V(α)4.2 bound specifically to I-A(u) expressed on the surface of a transfected thymoma cell line. Modifications in the amino acid residues located within the three complementarity-determining regions (CDRs) of the V(α) domain did not markedly affect this interaction. However, mutation of glutamic acid to alanine at position 69 of the fourth hypervariable region (HV4α) significantly increased the binding. Antibody inhibition studies suggested that the binding site was partly contributed by a region of the β chain of I-A(u). Furthermore, the binding of V(α)4.2 to the MHC molecule was dependent on the nature of the peptide bound in the groove. Soluble V(α)4.2 specifically inhibited the activation of TCR transfectants by I-A(u)-expressing cells pulsed with an N-terminal peptide of myelin basic protein. V(α)4.2 also bound to MHC class II-expressing spleen cell populations from mice of the H-2(u) and H-2(d) haplotypes. The binding of V(α)4.2 to I-A molecules might explain the immunoregulatory effects reported previously for TCR α chains. This V(α)4.2 interaction may also be relevant to models of antigen presentation involving the binding of intact proteins to MHC class II molecules followed by their processing to generate epitopes suitable for T cell recognition.</p
Induction of a type 1 regulatory CD4 T cell response following V<sub>β</sub>8.2 DNA vaccination results in immune deviation and protection from experimental autoimmune encephalomyelitis
No full textDNA vaccination has been used to generate effective cellular as well as humoral immunity against target antigens. Here we have investigated the induction and involvement of regulatory T cell (Treg) responses in mediating prevention of experimental autoimmune encephalomyelitis (EAE), following vaccination with plasmid DNA encoding the TCR Vβ8.2 chain predominantly displayed on disease-causing lymphocytes. Vaccination with DNA encoding the wild-type TCR results in priming of type 1 CD4 Treg and skewing of the global response to myelin basic protein in a Th2 direction, leading to significant protection from disease. In contrast, vaccination with mutant DNA encoding altered residues critically involved in recognition by the Treg results in priming of a type 2 regulatory response which fails to mediate immune deviation or protection from EAE. Control mice immunized with DNA, encoding TCR with changes at an irrelevant site, were protected from antigen-induced disease. Furthermore, protection can be transferred into naive recipients with CD4 Treg from wild-type DNA-immunized mice but not from animals vaccinated with the mutant DNA. These data suggest that vaccination with plasmid DNA encoding one or multiple Vβ genes can be exploited to enhance natural regulatory responses for intervention in autoimmune conditions.</p
A role for the region encompassing the c'' strand of a TCR Vα domain in T cell activation events
No full textThe distinct strand topology of TCR Vα domains results in a flatter surface in the region encompassing the c' strand than the corresponding region in Ig V domains. In the current study a possible role for this region in T cell activation has been investigated by inserting a potential glycosylation site at Vα residue 82. This residue is in proximity to the c'' strand and distal to the putative interaction site for cognate peptide:MHC ligand. An additional N-linked carbohydrate at this position would create a protrusion on the Vα domain surface, and this may interfere with TCR aggregation and/or recruitment of signaling molecules. The modified TCR has been expressed in transfected T cells, and the phenotype following stimulation has been compared with that of cells expressing the wild-type TCR. The mutation has significant effects on activation-induced cell death and TCR internalization, but, unexpectedly, does not affect IL-2 secretion. Furthermore, analyses with tetrameric, peptide:MHC class II complexes suggest that the mutation decreases the ability of the TCR to aggregate into a configuration compatible with avid binding by these multivalent ligands.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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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