bluuebunny/crossref_metadata_2025_split huggingface dataset:
T cell receptor Vα bias can be determined by TCR‐contact residues within an MHC‐bound peptide
Authors: STERRY SANDRA J. , KELLY JANICE M. , TURNER STEPHEN J. , CARBONE FRANCIS R. 
Published: July 2007

SummaryMany antigen‐specific T cell responses show profound V‐region biases in one or both chains of the TCR αβ heterodimer. We have examined how changes in residues within an MHC‐bound peptide can influence V‐region selection. Single‐chain TCR transgenic mice were derived using a β‐chain specific for the Kb‐restricted peptide from ovalbumin, OVA257‐264 Transgenic T cells were stimulated in vitro using OVA257‐264 or a single residue variant having a lysine to aspartic acid substitution at determinant position 7 (7D). Recent crystallographic analyses have shown that this variant residue is involved in direct contact with the TCR. Sequence analysis of the T cell populations showed that the majority OVA257‐264 specific T cells used Vα10‐positive TCR while the majority of the 7D‐specific TCR expressed the Vα4 element. In both peptide responses we found that some cell lines appeared to be made up of more than one clone expressing the same Vα sequence but having limited variation at the V‐J junction. These results show that the TCR contact residues within the target peptide can influence V‐region bias and suggest that the first and second hypervariable regions of the TCR are directly or indirectly involved in determining peptide specificity.
Production of monoclonal antibodies specific to the carboxyl terminal region of the 85 kDa subunit of phosphatidylinositol 3‐kinase: Use of the antibodies in recognition of mutant p85
Authors: DADUANG SAKDA , NAGATA SATOSHI , MATSUDA MICHIYUKI , YAMORI TAKAO , ONODERA KAZUKIYO , FUKUI YASUHISA 
Published: July 2007

SummaryWe have established two hybridomas producing mAb to the carboxyl terminal region of phosphatidylinositol‐3 kinase 85 kDa subunit type α (p85α). Analysis using deletion mutants of p85 revealed that epitopes for the two mAb were located on the border of the src homology 2 (SH2) sequence located at the carboxyl end of p85. They immunoprecipitated free p85 efficiently, but reactivity to p85 bound to pi 10 was very weak. Together with the mAb which we have reported previously, a panel of mAb that covered the various parts of p85α was obtained. Using this panel, we characterized two mutants of p85 (70 and 50 kDa) expressed in the human colon carcinoma cell line, HCC2998. No wild‐type p85 was detected in these cells. A mAb specific to the carboxyl terminal region detected p70 but not p50, suggesting that this region is missing in p50. The panel of mAb is a useful tool to use to analyse mutant forms of p85.
The one signal theory of B cell activation revisited: A role for surface immunoglobulin in regulating T‐independent antibody responses?
Authors: MAMCHAK ALUSHA A , HODGKIN PHILIP D 
Published: July 2007

SummaryEarly theories of antibody production by B cells achieved considerable success in predicting B cell behaviour with simple deductive models. One such model, the one signal theory, postulated that the antigen receptor on B cells played only a passive non‐signalling role in focusing non‐specific activating signals to the B cell surface. This prediction is at least partially consistent with recent discoveries concerning the helper signals delivered to B cells by T cells. Here, we re‐examine the foundation of this theoretical prediction with the benefit of recent information. The experimental basis for the theory was a study of B cell activation by LPS and, in particular, the interpretation of a bell‐shaped dose‐response curve. The logic applied is appropriate to explain some, but not all, forms of B cell behaviour because, as is now clear, the role played by the antigen signal varies depending upon the method of activation. This re‐examination suggests an alternative interpretation of the LPS‐induced bell‐shaped curves that incorporates a role for an antigen signal. If correct, the mechanism would ensure that T‐independent responses are drawn from low affinity precursors.
Immunohistological staining of lymphoid tissue in four Australian marsupial species using species cross‐reactive antibodies
Authors: HEMSLEY SW , CANFIELD PJ , HUSBAND AJ 
Published: July 2007

SummaryAntibodies raised against evolutionarily conserved intracytoplasmic peptide sequences of human T and B lymphocyte antigens and an antibody raised specifically against koala serum IgG were assessed for their capacity for immunoperoxidase staining of formalin fixed lymphoid tissues of koalas (Phascolarctos cinereus), common brushtail possums (Trichosurus vulpecula), common ringtail possums (Pseudocheirus peregrinus) and tammar wallabies (Macropus eugenii). Utilizing microwave pretreatment and a streptavidin biotin‐horseradish peroxidase method for histochemical staining, polyclonal anti‐human CD3 (for T cells), monoclonal anti‐human CD5 (for T cells), monoclonal anti‐human CD79b cy (for B cells) and polyclonal anti‐koala IgG (for plasma cells) consistently stained lymphoid elements in a wide range of tissues from all four marsupial species. Monoclonal anti‐human CD79a cy (for B cells) stained lymphoid elements in only brushtail possums.This is the first report of Immunohistological staining of lymphocytes m Australian marsupials, thereby vastly increasing the scope for immunological studies in these species.
Cytokine mRNA expressed in tuberculin skin test biopsies from BCG‐vaccinated and Mycobacterium bovis inoculated cattle
Authors: NG KEE H , WATSON JAMES D , PRESTIDGE ROSS , BUDDLE BRYCE M 
Published: July 2007

SummaryTo obtain a better understanding of the delayed‐type hypersensitivity reaction to Mycobacterium bovis, we measured the expression of cytokine mRNA from tuberculin skin test biopsies of cattle. Non‐vaccinated and BCG‐vaccinated cattle were inoculated intratracheally with a low dose of virulent M. bovis or sham‐inoculated and 20 weeks later were skin tested with tuberculin. At necropsy 1–2 weeks later, tuberculous lesions were found in six of the nine non‐vaccinated and three of the nine BCG‐vaccinated animals. All of the lesioned and the majority of the non‐lesioned M. bovis inoculated cattle showed a distinct skin swelling response to tuberculin, irrespective of vaccination. However, cattle with tuberculous lesions displayed larger skin swelling responses than non‐lesioned cattle. Tuberculin‐induced expression of IFN‐γ, IL2, IL4, IL10 and TNF‐α mRNA occurred in the skin biopsies of all of the lesioned, M. bovis inoculated animals except for an absence of tuberculin‐induced TNF‐α mRNA expression in two animals. A lower proportion of the non‐lesioned M. bovis inoculated cattle displayed tuberculin‐induced expression of the five cytokine mRNA. There was no evidence of a unique pattern of cytokine expression which could be used to distinguish between diseased and protected animals. By 28 weeks after vaccination, the three BCG‐vaccinated, sham‐inoculated cattle displayed minimal skin swelling response to tuberculin, but tuberculin‐induced expression of IFN‐γ, IL2, IL4, TL10 and TNF‐α mRNA was observed in skin biopsies of all of these animals. The pattern of cytokine mRNA expressed in the tuberculin skin test reaction site of cattle appeared to be typical of a mixed T helper O‐like cell phenotype response and there was no clear‐cut relationship between the size of the tuberculin skin swelling response and cytokine mRNA expression.
Peritoneal cavity CD5 (Bla) B cells: Cytokine induced IgA secretion and homing to intestinal lamina propria in SCID mice
Authors: BEAGLEY KW , MURRAY AM , McGHEE JR , ELDRIDGE JH. 
Published: July 2007

SummaryThe mouse peritoneal cavity contains a unique population of B cells (Bla) with a high IgM/low IgD ratio, CD5+ (Lyl), MAC‐1 + phenotype. These cells arise early in ontogeny, utilize a limited repertoire of immunoglobulin V genes, produce polyreactive IgM antibodies and have been implicated as the source of many auto‐reactive immunoglobulins. Recent data from chimeric mice suggest that this B cell population also contains the precursors of many IgA plasma cells found in the lamina propria of the small intestine. In the present study we have investigated the potential of this cell population to secrete IgA (and IgG) in response to various cytokines. IL‐5 alone, or in combination with IL‐2, greatly enhanced secretion of both IgG and IgA. Cytokine‐induced IgA secretion resulted from expansion of a subset of CD5 B cells co‐expressing sIgA. Adoptive transfer of CD5 B cells to severe combined immunodeficient (SCID) mice resulted in repopulation of lamina propria with sIgA+ B cells while peripheral lymph nodes contained only IgM+ and some IgG+ B cells. Transfer of CD5+ B cells also reconstituted serum IgM. IgG and IgA levels in recipient SCID mice. These studies demonstrate that CD5′ B cells have the potential to secrete IgA and IgG, immunoglobulins characteristic of mucosal and anamnestic responses, when cultured in vitro with the appropriate cytokines. These cells also give rise to IgA plasma cells in the intestinal lamina propria following adoptive transfer to SCID mice, further supporting the hypothesis that cells of this lineage may be important in immune responses at mucosal surfaces.
Genetic approaches to the study of cytokine regulation of mucosal immunity
Authors: RAMSAY ALISTAIR J 
Published: July 2007

SummaryEfforts to design effective mucosal vaccines have been hampered by an incomplete understanding of factors controlling the development of mucosal immunity. It is now clear, however, that T cell‐derived cytokines play a major role. Recent developments in ‘gene knockout’ technology have allowed the generation of strains of mice in which particular genes have been inactivated. The availability of mice rendered deficient for production of Th2 cytokines has facilitated studies of the induction and development of mucosal immune responses in the absence of these factors. We have used several genetic approaches, including cytokine‐deficient mice and recombinant vectors constructed to express genes for a range of different cytokines, to demonstrate the importance of these factors in the mucosa. Such genetic approaches appear to represent powerful tools for in vivo studies of the influence of cytokines in mucosal immunoregulation.
Altered calcium signal transduction in B‐1 malignant cells
Authors: DANG ANJU M , BALASUBRAMANYAM M , GARCIA ZENAIDA , RAVECHE ELIZABETH , GARDNER JEFFREY P 
Published: July 2007

SummaryLymphocyte proliferation is guided by receptor‐mediated signal transduction pathways that dictate the immunological response/clonality of that cell. We have previously reported that NZB‐derived malignant B‐1 cells, which serve as a murine model for human chronic lymphocytic leukaemia, demonstrate altered expression of surface IgM and CD45 signalling molecules, and a failure to proliferate following membrane IgM stimulation. To examine receptor‐mediated cytosolic calcium (Ca1) signalling in B cell leukaemia, we studied IgM‐induced Ca, responses in malignant B‐1 cells and B cells from non‐leukaemic mice. Basal Ca1 was slightly lower in malignant B‐l cells than in non‐leukaemic cells. Anti‐IgM stimulation induced a sustained increase in Ca1 to levels 1.3‐fold greater than basal Ca1 in conventional B cells. In contrast, leukaemic B‐1 cells demonstrated a sharp but transient rise in Ca1 followed by a gradual increase to levels 2.3‐fold greater than basal [Ca]1 Ca influx from extracellular sources contributed to the early and late Ca1 signal in both sets of cells. Pre‐incubation (2–30 min) with anti‐CD45 had no effect on basal Ca, or the anti‐IgM Ca1 signal in B cells, but reduced the Ca1 transient in malignant B‐1 cells. Additional experiments characterized the effects of phosphorylation/dephosphorylation events on the Ca1 profile following anti‐IgM stimulation. Protein tyrosine kinase inhibitors decreased the anti‐IgM‐induced Ca1 transient in malignant B‐1 cells by 80%, but only moderately affected 40% the Ca1 response in non‐leukaemic B cells. Protein tyrosine phosphatase inhibitors and protein kinase C (PKC) activators attenuated the Ca1 response to the same degree in normal and leukaemic B cells. These results show that Ca1 signalling differs widely between non‐malignant B cells and malignant B‐1 cells, and that tyrosine phosphorylation and CD45 modulation of IgM signalling are involved in the altered Ca1 responses in malignant B‐1 cells.
Dendritic cell presentation of PPD and 19 kDa protein of Mycobacterium tuberculosis and emergent T helper cell phenotype
Authors: BAIRD MARGARET A , HART DEREK NJ , ABERNETHY NEVIN , WATSON JAMES D 
Published: July 2007

SummaryProtection against infection with Mycobacterium tuberculosis is preferentially associated with the development of the T helper 1 subset, IFN‐γ production and a cell‐mediated response, rather than with T helper 2 cells, 4 (IL‐4) and antibody production. The type of APC interacting with T cells responsive to mycobacterial peptides may influence which of these responses predominates. This investigation focuses on the role of dendritic cells (DC) because they are the most potent APC in both primary and recall immune responses. Our results show that splenic DC‐enriched suspensions prepared from C57BL/6 mice and pulsed with either purified protein derivative (PPD) or the immunodominant 19 kDa protein from M. tuberculosis, can activate antigen‐primed T cells in vitro, whereas spleen cell suspensions depleted of DC cannot. DC pulsed with PPD or 19 kDa antigen are able to prime naive T cells in vivo. Supernatants collected from cultures containing T cells from mice injected with PPD‐pulsed DC and then challenged in vitro with PPD‐pulsed DC were found to contain more IL‐2 and IFN‐γ than those from control mice which received either DC or PPD alone. No such antigen‐specific IFN‐γ response occurred if DC pulsed with 19 kDa were used in place of PPD‐pulsed DC. IL‐4 was not detected in any of the culture supernatants. We conclude that DC can induce production of cytokines associated with a protective immune response when presenting peptides derived from heterogeneous mycobacterial antigens but not when exposed to the single 19 kDa immunodominant protein.
Hierarchy of T cell antigen receptor assembly
Authors: MANOLIOS NICHOLAS 
Published: July 2007

SummaryThe formation of partial complexes in an African green monkey kidney cell line (COS cells) has been used to examine assembly of newly synthesized T cell antigen receptor (TCR) chains. The identification of assembly interactions between multiple subunits and the formation of higher order subcomplexes has led to the development of a model for the hierarchy of subunit assembly leading to a complete TCR. These assembly interactions suggest likely nearest neighbour relationships in the assembling structure and probably reflect the quarternary structure ofthe TCR complex. This may be important when examining the association of other molecules with TCR proteins or when trying to discern structural components involved with signal transduction.
Transcriptome profiling of the response of Mycosphaerella graminicola isolates to an azole fungicide using cDNA microarrays
Authors: COOLS HANS J. , FRAAIJE BART A. , BEAN TIM P. , ANTONIW JOHN , LUCAS JOHN A. 
Published: July 2007

SUMMARYResistance to azole antifungals is a major problem in the control of diseases caused by fungal pathogens of both humans and plants. Potential for the development of azole resistance in the wheat leaf blotch pathogen Mycosphaerella graminicola, the causal agent of the most economically significant foliar disease of wheat in north‐western Europe, is now of particular concern after the recent emergence of widespread resistance to quinone outside inhibitor fungicides. Using a cDNA microarray representing around 25% of the genome, we have profiled the transcriptional response of M. graminicola to epoxiconazole, currently the most widely used azole fungicide on cereal crops. By comparing the transcription profiles of two M. graminicola isolates with contrasting sensitivities to epoxiconazole we show qualitative and quantitative differences in differentially expressed genes, including those involved in ergosterol biosynthesis, mitochondrial respiration and transport mechanisms. This represents the first study investigating the response of a plant pathogenic fungus to a fungicide using cDNA microarray technology.
Relationship between glutathione S‐transferase gene polymorphisms and enzyme activity in Hong Kong Chinese asthmatics
Authors: Mak J. C. W. , Ho S. P. , Leung H. C. M. , Cheung A. H. K. , Law B. K. W. , So L. K. Y. , Chan J. W. M. , Chau C. H. , Lam W. K. , Ip M. S. M. , Chan‐Yeung M. 
Published: July 2007

SummaryBackground
Asthma is a disease associated with oxidative stress. The glutathione S‐transferases (GST) are a group of enzymes that protect cells from oxidative stress. Functional genetic polymorphisms of GST genes (GSTT1, GSTM1 and GSTP1) have previously been reported.Objective
To investigate the association of GST gene polymorphisms and its enzyme activity with the risk of asthma in Hong Kong Chinese adults.Methods
An age‐ and smoking status‐matched case–control study was carried out on 315 patients with asthma and 315 healthy controls. Genotyping was carried out on genomic DNA using the PCR and/or restriction fragment length polymorphism (PCR‐RFLP). Plasma GST activity was measured by fluorometric assay.Results
The distribution of various genotypes or alleles of the GSTT1, GSTM1 and GSTP1 was not significantly different between patients with asthma and healthy controls. The GSTM1 null genotype was found to be protective from the development of asthma in atopic subjects (odds ratios 0.55, 95% confidence interval 0.34–0.90; P=0.017). However, there was no association between GSTT1 and GSTM1 null genotypes and enzyme activity. GSTP1 codon 105 Val variants led to reduced plasma GST activity in healthy controls. Asthma patients had elevated plasma GST activity compared with healthy controls irrespective of their genotypes (P<0.001).Conclusion
Our data suggest that among atopic subjects, the GSTM1 null genotype is associated with a decreased risk for asthma despite increased level of plasma GST activity in asthma, but it could not distinguish whether this increase is a potentially protective compensatory effect or a pathogenic factor.
Maternal–fetal interaction: preconception immunization in mice prevents neonatal sensitization induced by allergen exposure during pregnancy and breastfeeding
Authors: Fusaro Ana E. , Brito Cyro A. , Victor Jefferson R. , Rigato Paula O. , Goldoni Adriana L. , Duarte Alberto J. S. , Sato Maria N. 
Published: July 2007

SummaryAllergen exclusion measures during pregnancy and lactation have been given consideration in studies of primary allergy prevention but complete avoidance of mother/neonatal allergen exposure has proven to be a difficult procedure. To evaluate a strategy to prevent allergen sensitization in early life in mice, we first established a neonatal model with ovalbumin sensitization through maternal allergen exposure during pregnancy or breastfeeding. The modulatory potential of preconception immunization was investigated on the neonatal development of subsequent allergic responses to maternal allergen exposure. Herein, we demonstrate that immunized mothers exposed to antigen during pregnancy or breastfeeding underwent intense vertical transmission of antibodies, including immunoglobulin G (IgG) in complex with ovalbumin and IgG1 antibody with anaphylactic function. It was further shown that maternal immunization efficiently decreased the passage of free antigens through breastfeeding and inhibited the enhanced IgE antibody response after postnatal antigen exposure. In addition, antenatal immunization decreased the antigen‐specific proliferative response of immunized neonates, in parallel with profound downmodulatory effects on both the activation and differentiation of T and B cells after a non‐specific stimulus and cytokine production. These findings showed that early life sensitization, subsequent to maternal allergen exposure during both the prenatal and postnatal periods, could be avoided by preventive vaccination of the mother.
Interleukin‐6 is responsible for aberrant B‐cell receptor‐mediated regulation of RAG expression in systemic lupus erythematosus
Authors: Hillion Sophie , Garaud Soizic , Devauchelle Valérie , Bordron Anne , Berthou Christian , Youinou Pierre , Jamin Christophe 
Published: July 2007

SummaryDefective regulation of secondary immunoglobulin V(D)J gene rearrangement promotes the production of autoantibodies in systemic lupus erythematosus (SLE). It remains unclear, however, whether the regulation of the recombination‐activating genes RAG1 and RAG2 is effective in SLE. RAG1 and RAG2 messenger RNA expression was analysed before and after in vitro activation of sorted CD19+ CD5– B cells with anti‐immunoglobulin M antibodies, in 20 SLE patients and 17 healthy controls. The expression of CDK2 and p27Kip1 regulators of the RAG2 protein, were examined. The levels of interleukin‐6 (IL‐6) and its influence on RAG regulation were also evaluated in vitro. SLE patients had increased frequency of RAG‐positive B cells. B‐cell receptor (BCR) engagement induced a shift in the frequency of κ‐ and λ‐positive cells, associated with a persistence of RAG messenger RNA and the maintenance of RAG2 protein within the nucleus. While expression of the RAG2‐negative regulator CDK2 was normal, the positive regulator p27Kip1 was up‐regulated and enhanced by BCR engagement. This effect was the result of the aberrant production of IL‐6 by SLE B cells. Furthermore, IL‐6 receptor blockade led to a reduction in p27Kip1 expression, and allowed the translocation of RAG2 from the nucleus to the cytoplasm. Our study indicates that aberrant production of IL‐6 contributes to the inability of SLE B cells to terminate RAG protein production. Therefore, we hypothesize that because of constitutive IL‐6 signalling in association with BCR engagement, SLE B cells would become prone to secondary immunoglobulin gene rearrangements and autoantibody production.
Evidence for size and sex‐specific dispersal in a cooperatively breeding cichlid fish
Authors: STIVER K. A. , DESJARDINS J. K. , FITZPATRICK J. L. , NEFF B. , QUINN J. S. , BALSHINE S. 
Published: July 2007

AbstractAfrican Great Lake cichlid populations are divided into thousands of genetic subpopulations. The low gene flow between these subpopulations is thought to result from high degrees of natal philopatry, heavy predation pressure, and a patchy distribution of preferred habitats. While predation pressure and habitat distribution are fairly straightforward to assess, data on dispersal distances and rates are scarce. In fishes, direct observations of dispersal events are unlikely, but dispersal can be studied using molecular markers. Using seven microsatellite loci, we examined dispersal in the cooperatively breeding cichlid fish, Neolamprologus pulcher. As this species is found in well‐defined groups clustered into subpopulations, we could assess dispersal on a narrow (within subpopulation) and broad (between subpopulation) scale. While fish were generally more related to others in their own subpopulation than they were to fish from other subpopulations, large males diverged from this pattern. Large males were more related to other large males from different subpopulations than they were to large males from their own subpopulation, suggesting more frequent dispersal by large males. Across subpopulations, relatedness between large males was higher than the relatedness among large females; this pattern was not detected in small males and small females. Within a subpopulation, individuals appeared to be preferentially moving away from relatives, and movement was unrestricted by the physical distance between groups. Our results highlight the importance of examining multiple spatial scales when studying individual dispersal biases.