bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allelic exclusion in transgenic mice expressing a heavy chain disease‐like human μ protein
Authors: Corcos Daniel , Iglesias Antonio , Dunda Olga , Jami Jacques 
Published: March 2007

AbstractHeavy chain diseases (HCD) are neoplastic proliferations of B cells which secrete truncated immunoglobulin heavy chains without associated light chains. These proteins are encoded by mutated genes which may also give rise to truncated membrane immunoglobulins. The neoplastic cells proliferate in vivo although they cannot bind any antigen, due to deletions in the variable domain of their antigen receptors. The reason for the clonal proliferation of HCD cells and the biological effects of the truncated membrane‐bound chains are presently unknown. We wanted to determine whether the expression of HCD proteins would interfere with B cell development. To this end we made transgenic mice with a human μ gene, lacking the VDJ exon, that encodes a protein similar to that produced in two cases of HCD. Transgenic mice were also produced with a similar construct but encoding only the membrane‐bound form of the truncated μ chain. Transgene encoded Cμ proteins are expressed on the cell surface without associated light chains and are responsible for allelic exclusion of murine heavy chains.
Induction of antigen‐specific CD8+ cytolytic T cells by the exogenous bacterial antigen streptolysin O in rhesus monkeys
Authors: Chizzolini Carlo , Millet Pascal G. , Olsen‐Rasmussen Melissa A. , Collins William E. 
Published: March 2007

AbstractWe have characterized the T cell responses induced by streptolysin O (SLO), a sulfydryl‐activated hemolysin secreted by streptococci, by applying long‐term in vitro culture and cloning rhesus monkey (Macaca mulatta) T cells. T cell lines specific for SLO were obtained from three rhesus monkeys. These T cell lines required autologous antigen‐presenting cells (APC) to proliferate in response to SLO and did not respond to purified protein derivative. Phenotypic analysis showed that the cells from two of three SLO‐specific T cell lines were more than 85% CD3+CD4−CD8+ after prolonged in vitro culture. The rh 1842 CD8+ T cell line proliferative response to SLO was inhibited by the addition of anti‐major histocompatibility complex (MHC) class I and anti‐CD8 but not of anti‐MHC class II and anti‐CD4 monoclonal antibody (mAb). This cell line was able to lyse P815 target cells in the presence of anti‐CD3 mAb and did not show natural killer activity. Moreover, specific lysis of autologous but not allogeneic non‐rosetting E− cell targets pulsed with SLO was observed. Such lysis was inhibited by the addition of anti‐MHC class I mAb.In the attempt to identify the restriction elements involved in SLO presentation APC from six unrelated rhesus monkeys and three humans were used. A CD4+ rh 1842 T cell clone responded when SLO was presented by one of six, and a CD8+ rh 1842 T cell clone by four of six rhesus monkeys APC. Both CD4+ and CD8+ T cell clones did not respond when SLO was presented by human APC. However, both clones responded when APC from all donors were used in conjunction with anti‐CD3 mb. Furthermore, SLO required active processing to be presented to CD4+ and CD8+ T cell clones as glutaraldehyde fixation of APC before but not after antigen pulsing inhibited T cell proliferation.The SLO‐specific CD8+ cytolytic T cells described here could play a role in the regulation of the immune response occurring during streptococcal infections and/or could participate in the pathogenesis of poststreptococcal nonsuppurative sequelae.
Comparison of class I‐ and II‐restricted T cell recognition of the identical peptide
Authors: Perkins David L. , Berriz Gabriel , Wang Yunsheng , Smith John A. , Gefter Malcolm L. 
Published: March 2007

AbstractThere is structural and functional evidence that both class I‐ and II‐restricted T cells recognize short processed peptides bound to MHC molecules. Although the structural conformation of bound peptides remains unknown, no evidence of distinct structural motifs of class I‐ or class II‐restricted peptides has been described. Conversely, two algorithims proprosed to predict T cell epitopes, and based on primary amino acid sequence or tertiary structure, are both compatible with many observed class I‐ and class II‐restricted peptides. We previously identified eight class I‐restricted peptides which were also recognized by class II‐restricted T cells. Based on functional and direct binding studies, additional examples of peptides with both class I and II restrictions have been identified. In this study, we have directly compared the fine specificity of T cell recognition of a single epitope in a single mouse strain in the context of both class I‐ and class II‐restricted responses. Based on a panel of analogue peptides with amino acid substitutions and peptides of various lengths, we observed several striking similarities in the recognition patterns of both class I‐ and class II‐ restricted T cells. In addition, some characteristics of recognition were different in the two systems indicating that the recognition processes were similar but not identical.
Signaling requirements for the expression of the transactivating factor NF‐AT in human T lymphocytes
Authors: Hivroz‐Burgaud Claire , Clipstone Neil A. , Cantrell Doreen A. 
Published: March 2007

AbstractA protein called nuclear factor of activated T cells (NF‐AT) binds to DNA sequences within the enhancer region of the interleukin 2 (IL 2) gene and appears necessary for both the inducibility and T cell specificity of IL 2 expression. IL 2 production is regulated by multiple signals including those generated via activation of the T cell antigen receptor complex (TcR/CD3), CD2 antigen, protein kinase C (PKC) or elevation of intracellular free calcium concentration ([Ca2+]i). We have, therefore, explored the role of these different stimuli in regulating the nuclear expression of NF‐AT in human peripheral blood‐derived lymphocytes. Results presented herein indicate that maximal expression of NF‐AT in T cells requires at least two signals: PKC activation and TcR/CD3 or CD2 triggering, [Ca2+]j increases and TcR/CD3 or CD2 triggering. Data are presented that indicate that either the [Ca2+]i or PKC signal generated via the TcR/CD3 complex would not alone induce NF‐AT expression, and that the TcR/CD3 complex probably regulates NF‐AT expression because of its ability to regulate multiple intracellular signals in T cells, and not via any single biochemical event. The combination of CD2 mAb GT2/OKT11 used in the present study to trigger the CD2 antigen is able to act in synergy with phorbol 12,13‐dibutyrate or ionomycin to induce NF‐AT expression. However, these CD2 mAb do not elevate [Ca2+]i or activate PKC, suggesting that signals other than [Ca2+]i or PKC can regulate NF‐AT expression in peripheral blood‐derived T cells.
Phosphorylation of the β‐subunit of CD11/CD18 integrins by protein kinase C correlates with leukocyte adhesion
Authors: Valmu Leena , Autero Matti , Siljander Fia , Patarroyo Manuel , Gahmberg Carl G. 
Published: March 2007

AbstractAdhesion of activated leukocytes to cells is of critical functional importance. The adhesion is known to be mediated mainly by the CD11/CD18 integrins, also known as leukocytic cell adhesion molecules, or Leu‐CAM. We have now studied the phosphorylation of Leu‐CAM by protein kinase C and the correlation of phosphorylation with the generation of the adhesive phenotype among human peripheral blood mononuclear leukocytes during cell activation. We here show that a good correlation exists between the phosphorylation of the β subunit of Leu‐CAM (CD18), and the extent of cell‐to‐cell adhesion. The phosphorylated CD18 subunit was associated with both CD11a and CD11b. Purified protein kinase C was able to phosphorylate the β subunit of isolated Leu‐CAM in vitro. The phosphorylation occurred mainly on serine residues.
V genes of oxazolone antibodies in 10 strains of mice
Authors: Kaartinen Matti , Solin Marja‐Liisa , Mäkelä Olli 
Published: March 2007

AbstractOne pair of V genes (Vx45.1 and V11) code for a great portion of phenyloxazo‐lone (anti‐phOx) antibodies in 10 strains of mice. This combination replaces the first‐known major combination VHOx1‐VxOx1 in some strains, and is important in most strains. C57BL/10 and SJL mice have an additional subset of antibodies encoded by genes Vx45.1 and V13 (a relative of V11).All three genes involved (Vx45.1, V11 and V13) have „allelic”︁ variation. Four alleles of V11 were found, one in Igh haplotypes a, c and g, the second in haplotypes d, j and n, the third in b, and the fourth in f. The most distant alleles d,j,n and f had 10 nucleotide differences out of 429 determined (97.7% homology). Only one allele of the V13 gene was found from anti‐phOx hybridomas but two others have been published. Three alleles of the Vx45.1 gene were found; one in NZB mice (Igx haplotype b) another in CE (haplotype f), and the third in eight strains including representatives of three Igx haplotypes (a, c and e). The three alleles had >99.0% homology.The V11 and V13 genes that code for anti‐phOx antibodies in C57BL/10 and SJL mice were different from the related genes found from the C57BL/10 germ line. C57BL/10 mice must have a chromosome bearing two V11 and two V13 genes. RF mice were found to have two V11 genes, and both code for anti‐phOx antibodies.Our data show that the majority of antibodies in the anti‐phOx response are encoded by the same restricted collection of V genes in most mouse strains. Antibody responses appear to be no less heritable than other functions of the body.
The role of C5a and antibody in the release of heparan sulfate from endothelial cells
Authors: Platt Jeffrey L. , Dalmasso Agustin P. , Lindman Bonnie J. , Ihrcke Nathan S. , Bach Fritz H. 
Published: March 2007

AbstractThe activation of endothelial cells is thought to contribute to the host response to infection and to the pathogenesis of autoimmune disease. It was recently shown that antibody and complement can activate endothelial cells leading to cleavage and release of heparan sulfate from the cells. We show here that release of heparan sulfate from endothelial cells is mediated by antibody and the complement fragment C5a and that assembly of the membrane attack complex and lysis of endothelial cells is not necessarily involved. These data suggest that the generation of C5a in conditions such as autoimmunity and infection in which anti‐endothelial cell antibodies may also be present, might amplify tissue injury by a novel mechanism involving endothelial cell activation and loss of heparan sulfate mediated by antibody and C5a.
Exact prediction of a natural T cell epitope
Authors: Rötzschke Olaf , Falk Kirsten , Stevanovic Stefan , Jung Günther , Walden Peter , Rammensee Hans‐Georg 
Published: March 2007

AbstractT lymphocytes recognize their antigen as peptides associated with major histocompatibility complex (MHC) molecules. Peptides naturally presented by MHC class I molecules are uniform in length and have a specific motif, both defined by the respective MHC allele (Falk, K. et al. Nature 1991. 351: 290). These allele‐specific motifs should allow exact prediction of natural T cell epitopes. H‐2Kb‐restricted epitopes, for example, have a length of eight amino acid residues and conserved anchor residues at positions 5 and 8. According to this information, we predicted the natural Kb‐restricted epitope of ovalbumin, thought to be contained in the 19‐mer IINFEKLTEWTSSNVMEER, to be SIINFEKL. Here we show that this prediction is correct. Thus, exact prediction of natural T cell epitopes is possible.
The λ/λ ratio in surface immunoglobulin molecules on B lymphocytes differentiating from DHJH‐rearranged murine pre‐B cell clones in vitro
Authors: Rolink Antonius , Streb Martin , Melchers Fritz 
Published: March 2007

AbstractThe expression of x and λ light chains in surface immunoglobulin (sIg) molecules on B lymphocytes differentiating from murine pre‐B cell clones in vitro was analyzed. The four pre‐B cell clones used represent a very early pre‐B cell stage. They have their heavy chain loci DJ rearranged and their light chain loci in germ‐line configuration. In order to grow in vitro, these clones require contact with stromal cells and the stimulatory activity of interleukin (IL) 7. Upon removal of IL 7 from the cultures, these clones differentiate within 3 days into sIg+ B cells. Between 7% and 12% of IgM+ B cells could be detected in these cultures. The majority (78%‐92%) of the IgM+ B cells co‐expressed x light chains. The percentage of λ light chain expressing B cells was below detectable level. Upon lipopolysaccharide (LPS) stimulation, the percentages of IgM+ B cells increased dramatically (from 32%‐64%). The majority (91%‐97%) of the IgM+ B cells express x chains, but a very small percentage (3.1%‐5.0%) express λ. A similarly high x/λ ratio was found in 418 hybridomas prepared from these LPS‐stimulated B cells (388 x+ and 30 λ+). Thus, the high x/λ ratio characteristic of the mouse peripheral B cell repertoire is already evident in the antigen‐independent transition from pre‐B to B cells.
Peptide loading of empty major histocompatibility complex molecules on RMA‐S cells allows the induction of primary cytotoxic T lymphocyte responses
Authors: De Bruijn Marloes L. H. , Schumacher Ton N. M. , Nieland John D. , Ploegh Hidde L. , Martin Kast W. , Melief Cornelis J. M. 
Published: March 2007

AbstractThe antigen processing‐defective mutant cell line RMA‐S expresses at the cell surface major histocompatibility complex (MHC) class I molecules devoid of peptide that can be efficiently loaded with exogenous immunogenic peptides. We now report that viral peptide‐loaded RMA‐S cells, unlike parental RMA cells, can induce primary cytotoxic T lymphocyte (CTL) responses in vitro, in a T helper cell‐independent fashion. This was shown for an H‐2Kb‐binding peptide of Sendai virus nucleoprotein and an H‐2Db‐binding peptide of adenovirus type 5 E1A protein with responding spleen cells of C57BL/6 mice, the strain of origin of RMA and RMA‐S cells. Primary Sendai peptide‐induced CTL lyse both peptide‐loaded and virus‐infected cells. Pre‐culture of RMA‐S cells at low temperature (22°–26°C), which increases the amount of empty MHC class I molecules at the cell surface, decreases the peptide concentrations required for the induction of primary CTL responses. Primary peptide‐specific CTL responses induced by peptide‐loaded RMA‐S cells are CD4+ cell‐ and MHC class II+ cell‐independent. CTL response induction is blocked by the presence of anti‐CD8 monoclonal antibody during culture. Direct peptide binding studies confirm the efficient loading of empty MHC molecules on RMA‐S cells with peptide and show 2.5‐fold more peptide bound per RMA‐S cell compared to RMA cells. An additional factor explaining the difference in primary response induction between RMA and RMA‐S cells is related to the CD8 dependence of these responses. MHC class I molecules occupied with irrelevant peptides (a majority present on RMA, largely absent on RMA‐S) may interfere in the interaction of the CD8 molecule with relevant MHC/peptide complexes. The results delineate a novel strategy of peptide based in vitro immunization to elicit CD8+ cytotoxic T cell responses.
Cells producing antibodies specific for myelin basic protein region 70–89 are predominant in cerebrospinal fluid from patients with multiple sclerosis
Authors: Martino Gianvito , Olsson Tomas , Fredrikson Sten , Hojeberg Bo , Kostulas Vasilios , Grimaldi Luigi M. E. , Link Hans 
Published: March 2007

AbstractCells secreting antibodies against guinea pig myelin and synthetic myelin basic protein (MBP) peptides were evaluated in cerebrospinal fluid (CSF) and blood from patients with multiple sclerosis (MS) and a variety of other neurological diseases (OND). The peptides used, reproducing amino acid sequences 1–20, 70–89, 108–126, or 157–166 of MBP, were selected on the basis of their hydrophilic and encephalitogenic properties. Low numbers of cells secreting IgG antibodies against myelin or each of the MBP peptides (about 1 per 50000) were detected in peripheral blood, with no difference between MS and OND. In CSF, cells secreting IgG antibodies to MBP 70–89 were more frequently (p = 0.007) detected in patients with MS (1/380 IgG‐secreting cells on average) than in patients with OND (1/2083 IgG‐secreting cells on average). The frequencies of cells secreting antibodies against myelin or the three other MBP peptides were similar in MS and OND. Thus, evaluation of B cell immunity at the cellular level indicates that MBP 70–89 is an immunodominant B cell epitope in MS. It is not clear whether this intrathecal anti‐MBP 70–89 IgG antibody response has any pathogenetic relevance in MS or is the result of myelin breakdown.
Cross‐linking of surface IgM activates NF‐xB in B lymphocyte
Authors: Rooney John W. , Dubois Patrice M. , Sibley Carol Hopkins 
Published: March 2007

AbstractIn B lymphocytes, cross‐linking of surface IgM activates changes in both the cell cycle and differentiation. In normal B cells and B cell tumors, many stimuli induce the activation of NF‐xB and its translocation from the cytoplasm to the nucleus. In this study we sought to determine if cross‐linking of surface IgM led to the activation of NF‐xB. Our results show that activation of B cells by cross‐linking anti‐IgM antibodies activated NF‐xB in the murine B lymphoid cell lines 70Z/3 and M12, and in the dense fraction of splenic cells. The activation of NF‐xB required optimal doses of anti‐IgM antibodies and took 5 to 10 min to reach maximal levels. Cross‐linking of IgM has also been shown to activate protein kinases including protein kinase C (PKC). To test wether PKC activation was required for NF‐xB translocation, we treated 70Z/3 cells for 18 h with phorbol 12‐myristate 13‐acetate, a procedure which depletes these cells of functional PKC. This treatment did not abrogate the nuclear translocation of NF‐xB following anti‐IgM cross‐linking. These results indicate that the nuclear translocation of NF‐xB is rapidly induced by surface IgM cross‐linking and that this activation appears to use a pathway which does not require PKC.
Polarized expression of major histocompatibility complex class I molecules in human endometrial and endocervical epithelial cells
Authors: Van Eijkeren Marion A. , Peters Peter J. , Geuze Hans J. 
Published: March 2007

AbstractThe localization of major histocompatibility complex (MHC) class I molecules in human endometrial and endocervical epithelial cells was studied with an immunogold technique on ultrathin cryosections. At the cell surface, MHC class I molecules are delivered solely to the basolateral plasma membrane in human epithelia. Therefore, only the basolateral domain of epithelial cells is capable of presenting antigen to MHC class I‐restricted cytotoxic T cells.
The CD56 adhesion molecule is the major determinant for detecting non‐major histocompatibility complex‐restricted cytotoxic mononuclear cells from the intestinal lamina propria
Authors: Van Tol Eric A. F. , Verspaget Hein W. , Pena A. Salvador , Kraemer Carlos V. Elzo , Lamers Cornelis B. H. W. 
Published: March 2007

AbstractIn this study, specific antibodies against natural killer (NK) cell surface markers identify these cells to be commonly present in normal intestinal mucosa of inflammatory bowel disease (IBD) and carcinoma patients. Cells expressing the CD56 adhesion molecule were found to be far more abundant than CD16+ cells. Functional studies revealed that cells mediating non‐major histocompatibility complex‐restricted cytotoxicity (NK activity) in the lamina propria express the CD56 surface antigen, whereas only a minority of this activity resides in the population with CD16 expression. This is in contrast with peripheral blood NK cells, which were found to be almost exclusively both CD16+ and CD56+. Moreover, in the lamina propria of the intestine we found CD3+ T lymphocytes not to be involved in spontaneous cell‐mediated killing of tumor cells.Considerably higher numbers of cells with the CD16 or CD56 surface markers were found to be present in normal mucosa of IBD patients compared with normal mucosa of carcinoma patients, which was also reflected in higher levels of cytotoxicity detected in lamina propria mononuclear cell preparations from normal IBD mucosa. Because of the disease‐related localization of the mucosa studied from both patient groups, i.e. ileum vs. colon, the observed differences may be related to tissue characteristics. Within the IBD group, relatively high levels of cytotoxicity were found in cell preparations from normal mucosa of Crohn's disease patients compared with ulcerative colitis patients, which might support the current concept that Crohn's disease affects the whole of the gastrointestinal tract.
Differences between T helper cell type I (Th1) and Th2 cell lines in signalling pathways for induction of contact‐dependent T cell help
Authors: Kawakami Kazuyoshi , Parker David C. 
Published: March 2007

AbstractB cells get help in the antibody response by presenting antigen to helper T (Th) cells. Upon antigen recognition, T cells produce lymphokines that act as growth and differentiation factors for B cells, but resting B cells require additional helper signals that depend on cell contact with an activated Th cell. Like lymphokine secretion, contact help must be induced by antigen recognition or antigen receptor cross‐linking in continuous Th cell lines. In the mouse, most CD4+ T cell lines can be classified into one of two stable differentiation states. Th1 or Th2, which produce different lymphokines and have different effector functions, activation requirements and cytoplasmic signalling mechanisms. This report demonstrates additional differences between Th1 and Th2 cell lines in the signalling pathways leading from the T cell antigen receptor to the induction of Th functions. In a system dependent on antigen presentation by B cells, B cell proliferation driven by Th2 cells but not Th1 cells was blocked by acute treatment with phorbol esters. Further experiments showed that phorbol esters blocked the induction of both contact help and lymphokine production in Th2 cells but not in Th1 cells. However, depletion of protein kinase C (PKC) activity by prolonged treatment of T cells with high concentrations of phorbol esters blocked induction of contact help and lymphokine production in Th1 cells but not in Th2 cells. These findings support the hypothesis that Th2 cells use a signalling pathway that is independent of PKC and that PKC activation can block this pathway. Since contact help and lymphokine secretion are affected in parallel, this difference between Th1 and Th2 cells probably reflects early events in the signalling pathway. Contact help and lymphokine production could be dissociated with cholera toxin and other cAMP agonists, but this dissociation could be explained by non‐cAMP‐related effects of cholera toxin on induction of contact help in Th2 cells, and by the direct effect of cAMP agonists on interleukin 2 gene transcription in Th1 cells reported by other laboratories.