bluuebunny/crossref_metadata_2025_split huggingface dataset:
Redistribution of critical major histocompatibility complex and T cell receptor‐binding functions of residues in an antigenic sequence after biterminal substitution
Authors: Reddehase Matthias J. , Koszinowski Ulrich H. 
Published: March 2007

AbstractResidues critical for establishing a trimolecular interaction with a major histocompatibility complex (MHC)‐encoded receptor and a T cell antigen receptor (TcR) were determined for an antigenic nonapeptide. The N‐terminal residue proved to be involved in binding of the peptide to both receptors and the C‐terminal residue was essential for MHC binding. While substitution of either of these critical terminal residues by alanine resulted in an almost complete loss of peptide antigenicity, simultaneous substitution of both created a new functional ligand for the same MHC molecule and the same TcR. Notably, in the biterminally substituted peptide, the core residues took on new roles in the trimolecular interaction in that a residue critical in the authentic nonapeptide for TcR binding became critical for MHC binding and former spacer residues became essential to various degrees for the interaction with either receptor or both. Thus, apparently, the loss of the terminal residues' contribution was at least partially compensated by a redistribution of the roles among the remaining residues. These results reflect a cooperative contribution of all residues of an antigenic peptide to its binding to both receptors and thus challenge a static definition of agretope and epitope as MHC and TcR binding sites.
Interleukin 4 induces CD8α expression on T cell receptor Vγ5 thymocytes
Authors: Leclercq Georges , De Smedt Magda , Plum Jean 
Published: March 2007

AbstractIt is generally accepted that most T cell receptor (TcR) γ/δ cells are CD4−CD8−. After in vitro culture; however, a low percentage of these cells express the CD8 α subunit. We show here that addition of recombinant interleukin (IL) 4 to IL 2‐cultured murine TcR Vγ5 thymocytes induces the expression of CD8α; CD8β is not expressed. Co‐addition of the anti‐IL 4 mAb 11B11 abrogates the induction of CD8 α expression, ruling out the possibility of a contaminant. Furthermore, we demonstrate that a substantial part of freshly prepared TcR Vγ5 thymocytes express CD8 α.
The function of human NK cells is enhanced by β‐glucan, a ligand of CR3 (CD11b/CD18)
Authors: Di Renzo Livia , Yefenof Eitan , Klein Eva 
Published: March 2007

AbstractCells responsible for the natural killer (NK) effect in the human blood can be collected in the low‐density lymphocyte subset and the majority of them express CR3. In addition to the iC3b binding site the CR3 molecules possess an epitope which binds β‐glucan. Ligands of this site can deliver activation signals to CR3‐carrying monocytes and neutrophils. We found that the function of NK cells was also potentiated by preincubation with β‐glucan. The treatment increased the proportion of target‐binding lymphocytes and of the damaged target cells in the conjugates. The monoclonal antibody OKM‐1, directed to the β‐glucan‐binding site of CR3, abrogated this effect. Another CR3‐reactive monoclonal antibody, M522, known to activate monocytes and neutrophils, enhanced the NK function.
Dissociation between syncytia formation and HIV spreading. Suppression of syncytia formation does not necessarily reflect inhibition of HIV infection
Authors: Pantaleo Giuseppe , Poli Guido , Butini Luca , Fox Cecil , Dayton Andrew I. , Fauci Anthony S. 
Published: March 2007

AbstractIn this study, we have observed that a disociation may occur in vitro between syncytia formation and HIV spreading‐Efficient HIV spreading and virus replication occurred either in HIV‐infected LFA‐1+ lymphocytes treated with anti‐LFA‐1 mAb or in HIV‐infected lymphocytes genetically deficient in LFa‐1, despite the fact that syncytia formation was completely suppressed. Therefore, these results indicate that syncytia formation cannot be used as the sole parameter to evaluate the spread of HIV in vitro.
Generation of long‐lived B cells in germ‐free mice
Authors: Förster Irmgard , Müller Werner , Schittek Birgit , Rajewsky Klaus 
Published: March 2007

AbstractIn the present study we have addressed the question of whether the composition of the peripheral B cell pool is similar in mice raised under conventional, specific pathogen‐free or germ‐free breeding conditions. For this purpose, the representation of various B lineage subsets was quantitated by flow cytometry and the lifespan of B cells analyzed by labeling dividing cells with the thymidine analogue 5‐bromo‐2′‐deoxyuridine in vivo. The results indicate that except for an increased fraction of CD45R(B220)dull B lineage cells in the bone marrow and a marginally faster turnover of splenic B cells in germ‐free compared to conventional mice, there is no obvious difference in the representation and turnover of B cells in the different kinds of mice. The data indicate that a stable pool of peripheral B cells is generated even in the absence of microbial stimulation.
Framework peptides from xIIIb rheumatoid factor light chains with binding activity for aggregated IgG
Authors: Hay Frank Charles , Soltys Andzriej Jan , Tribbick Gordon , Geysen H. Mario 
Published: March 2007

AbstractMost monoclonal human rheumatoid factors (RF) and some RF from rheumatoid patient's synovia are restricted in their light chains, using predominantly the xIIIb subfamily. Very few sequence differences are found between these light chains. Light chains with similar variable region framework sequences are also found in some mouse monoclonal RF derived from mice stimulated with lipopolysaccharide or secondarily immunized with protein antigens.There are two likely explanations for this restriction in framework sequences between the two species: (a) the sequences are important for the immunoregulation of RF production or (b) the sequences are concerned with the antibody binding specificity of the RF. We have examined overlapping octapeptides from the xIIIb light chain variable region and show that some framework peptides have the ability to bind aggregated IgG. Replacement of amino acids within the peak binding peptide have indicated the critical amino acids necessary for binding.
Components of an antigen‐/T cell receptor‐independent pathway of lymphokine production
Authors: Germann Tieno , Jin Shen‐Chu , Mattner Frank , Rüde Erwin 
Published: March 2007

AbstractThe general way to induce the synthesis of lymphokines by T cells is the stimulation through the T cell receptor (TcR) complex which results in an increase of intracellular [Ca2+] and in the activation of a tyrosine kinase as well as of protein kinase C. Lymphokine production induced via the TcR is inhibited by the immunosuppressive drug eyclosporin A (CsA). However, an alternative pathway of lymphokine production exists. Several T lymphocyte clones can synthesize interferon‐γ (IFN‐γ), granulocyte‐monocyte colony‐stimulating factor, and small amounts of interleukin (IL 3) when stimulated with syngeneic or allogeneic accessory cells (AC) plus IL 2. In contrast to the TcR pathway the alternative pathway does not require a rise of intracellular [Ca2+] and is insensitive to the effects of CsA. In this report we provide evidence for the involvement of T cell‐stimulating factor (TSF) ‐ a probably novel murine cytokine ‐ in the alternative pathway of lymphokine production. It is shown that fixation of the AC with carbodiimide or treatment of the AC with UV light greatly reduces their capacity to induce (in combination with IL 2) the synthesis of IFN‐γ by T cells. This function is restored by addition of TSF. Moreover, TSF alone (without IL 2) in combination with fixed AC can induce the synthesis of substantial amounts of IFN‐γ. Furthermore, TSF in combination with IL 2 can stimulate freshly isolated spleen cells to produce IFN‐γ. The target cell resides probably in the non‐B cell, non‐T cell population.
Production of interleukin 2 and interleukin 4 by immune CD4−CD8+ and their role in the generation of antigen‐specific cytotoxic T cells
Authors: Horvat Branka , Loukides Jill A. , Anandan Linda , Brewer Erin , Flood Patrick M. 
Published: March 2007

AbstractIn this report we investigated the production and role of interleukin (IL)2 and IL4 in the generation of antigen‐specific cytotoxic T cells (CTL). We used as our model the ultraviolet‐light‐induced epithelial tumor 1591, a highly immunogenic regressor tumor which evokes a strong cell‐mediated immune response leading to rejection. We show that IL2 and IL4 are differentially required for the development of optimal cytolytic activity to the 1591 tumor in primary and secondary in vitro splenic cultures. First, anti‐IL2 receptor monoclonal antibody (mAb) significantly decreased specific cytotoxicity in both primary and secondary splenic mixed lymphocyte‐tumor cell culture (MLTC) cultures, but anti‐IL4 mAb inhibited the cytotoxic responses only secondary and not primary cultures. Second, when supernatants from MLTC were tested for lymphokine activity, primary cultures produced only IL2 while secondary cultures produced both IL2 and IL4. Splenic cells were then depleted of CD4+ cells by negative selection, or enriched for CD8+ cells by positive selection, and tested for lymphokine production and requirements. CD8+ cells could not generate significant CTL activity in primary cultures, but could in secondary MLTC. The addition of mAb to either IL2 or IL4 significantly inhibited the generation of CTL by CD8+ cells in these secondary MLTC. CD8+ cells were also found to produce both IL2 and IL4 in secondary MLTC by functional and Northern blot analysis. The production of IL2 and IL4 by CD8+ cells occurs during different phases of culture, with IL2 being produced early (days 1 and 2) and IL4 late (days 3‐5). In addition, the requirement of CD8+ cells for both IL2 and IL4 is unique for that lymphokine. These results suggest that both IL2 and IL4 are both produced and required by CD8+ cells during secondary MLTC, and suggest an additional cellular source of IL4 production besides CD4+ T cells during antigen‐specific CTL responses.
Isolation of normal human follicular dendritic cells and CD4‐independent in vitro infection by human immunodeficiency virus (HIV‐1)
Authors: Stahmer Ingrid , Zimmer J. Pascal , Ernst Martin , Fenner Thomas , Finnern Ricarda , Schmitz Herbert , Flad Hans‐D. , Gerdes Johannes 
Published: March 2007

AbstractImmunohistological and electron microscopy studies of lymph nodes from patients infected with the human immunodeficiency virus 1 (HIV‐1) demonstrated that follicular dendritic cells (FDC), the antigen‐presenting cells of the B cell system, contain and may produce the virus. To elucidate the mode of infection of FDC with HIV‐1 in vitro we developed an improved method for the preparation of single‐cell suspensions of viable FDC with high purity (>90% FDC). These isolated FDC were subjected to human T cell leukemia virus IIIB infection, which was monitored after 4 days in culture using the polymerase chain reaction. We were able to demonstrate that normal human FDC are highly susceptible to infection by HIV‐1. Inhibition experiments with the monoclonal antibody OKT4a demonstrate that this infection is independent of the CD4 molecule.
The human interferon‐γ gene contains an inducible promoter that can be transactivated by tax I and II
Authors: Brown David A. , Nelson Forrest B. , Reinherz Ellis L. , Diamond Don J. 
Published: March 2007

AbstractT cells infected with the HTLV (human T cell leukemia virus)‐I and ‐II retroviruses often express the lymphokine interferon‐γ (IFN‐γ). We sought the molecular explanation for this phenomena by co‐transfecting the transactivator genes of these human retroviruses together with 5′ flanking sequences of the human IFN‐γ gene linked to a heterologous reporter gene. In the presence of phytohemagglutinin or anti‐T cell receptor monoclonal antibodies and phorbol 12‐myristate 13‐acetate, the IFN‐γ promoter is activated in human T cells, which can be further enhanced by co‐transfection of the tax I or II genes. Using Bal‐31 deletion analysis, we have found that induction by mitogens can be mapped to a region between −284 to −260 (bp) 5′ of the transcriptional start site, which is separable from the sequence(s) further upstream which transmit the synergistic transactivation by tax I or II.
Differential regulation of lymphokine production in mitogen‐stimulated murine spleen cells
Authors: Sander Birgitta , Cardell Susanna , Möller Göran , Möller Erna 
Published: March 2007

AbstractActivation of murine spleen cells in vitro with soluble anti‐CD3 monoclonal antibody and phorbol 12‐myristate 13‐acetate (PMA) induced an initial production of interleukin 2 (IL2), interferon‐γ (IFN‐γ), IL4 and IL5, followed by a refractory state during which the T cells did not produce lymphokines when stimulated with some common mitogens. The refractory state was long‐Jasting, depended on the presence of anti‐CD3 and PMA but could be reverted by incubation in fresh medium. Pokeweed mitogen (PWM) differed from other mitogens tested, since stimulation by PWM and PMA induced lymphokine production and proliferation also in the refractory cells. Furthermore, PWM stimulation selectively induced IL4 and IFN‐γ production but not IL2 and IL5, as detected by intracellular cytokine‐specific immunofluorescence and in situ hybridization for mRNA. The results indicate differential regulation of lymphokine production in primary lymphocytes.
Germinal center cells express bcl‐2 protein after activation by signals which prevent their entry into apoptosis
Authors: Liu Yong‐Jun , Mason David Y. , Johnson Gerald D. , Abbot Sandra , Gregory Christopher D. , Hardie Deborah L. , Gordon John , MacLennan Ian C. M. 
Published: March 2007

AbstractB cells undergo selection within germinal centers on the basis of their capacity to be activated by antigen held on follicular dendritic cells. Isolated germinal center B cells in culture kill themselves by apoptosis but this is prevented if their receptors for antigen are cross‐linked. In this study it is confirmed that almost all germinal center B cells, unlike other B cells, do not express the 25‐kDa protein encoded by the bcl‐2 oncogene. Cross‐linking the surface Ig of isolated germinal center cells causes them to express bcl‐2 protein. Two other stimuli which inhibit the entry of germinal center cells to apoptosis result in the expression of bcl‐2 protein. These stimuli are: (a) CD40 antibody and (b) recombinant 25‐kDa fragment of the CD23 protein plus recombinant interleukin 1α. Respectively, these induce germinal center cells to differentiate to resting B cells or plasmablasts. Dual‐fluorescence studies on small lymphocytes confirm the presence of bcl‐2 protein in mitochondria but show that this is also present in other extra‐nuclear areas.Burkitt lymphoma cells have a phenotype which indicates that they are neoplastic cells of germinal center origin. The expression of bcl‐2 protein by Burkitt lymphoma lines was also studied. Burkitt lines which retain the phenotype of fresh Burkitt lymphoma cells can be induced to enter apoptosis on culture with the Ca2+ ionophore ionomycin. These cells were found not to express bcl‐2 protein. By contrast, Burkitt lines which have drifted towards a lymphoblastoid cell line phenotype and are resistant to the induction of apoptosis express high levels of the bcl‐2 protein.The findings support the concept that the susceptibility of germinal center cells to entering apoptosis is associated with their lack of expression of bcl‐2 protein. Aberrant expression of bcl‐2 protein by some neoplastic germinal center cells may allow survival in situations where their normal counterparts die.
A single amino acid distinguishes the high‐responder from the low‐responder form of Fc receptor II on human monocytes
Authors: Clark Marcus R. , Stuart Susan G. , Kimberly Robert P. , Ory Peter A. , Goldstein Ira M. 
Published: March 2007

AbstractThe low‐affinity Fc receptor on human peripheral blood monocytes (FcγRIIA) is polymorphic with respect to its ability to bind murine IgG1. The two allelic forms of the receptor, high responder (HR) and low responder (LR), yield characteristic patterns after isoelectric focusing and react differently with the anti‐FcγRII monoclonal antibody (mAb), 41H16. We recently cloned cDNA encoding the extracellular domains of FcγRIIA on monocytes from one HR and two LR donors, and found that they differed at only a single base. The cDNA isolated from the HR donor had a G at position 519 and would be expected to encode an aginine at residue 133 in the mature protein, while the cDNA isolated from both LR donors had an A at position 519 and would be expected to encode a histidine at the same residue. To determine whether this single amino acid substitution actually accounts for the functional polymorphism involving FcγRIIA, we transfected COS cells with full‐length HR and LR FcγRIIA cDNA, and examined them for their ability to react with anti‐FcγRIIA mAb and to bind red blood cells (RBC) coated with either murine IgG2b or murine IgG1. Whereas COS cells transfected with either the HR cDNA or the LR cDNA reacted with the anti‐FcγRII mAb, IV.3, and bound murine IgG2b‐coated RBC, only COS cells transfected with the HR cDNA formed rosettes with murine IgG1‐coated RBC and reacted strongly with mAb 41H16. A total of nine LR donors were identified, and all were homozygous for the A substitution at position 519. We conclude that at an A at position 519 in the cDNA encoding FcγRIIA is the primary molecular basis for the LR form of the receptor, and that the amino acid at residue 133 determines whether FcγRIIA efficiently binds murine IgG1.
Human autoantibodies to lamin B receptor are also anti‐idiotypic to certain anti‐lamin B antibodies
Authors: Lassoued Kaiss , Danon Françoise , Brouet Jean‐Claude 
Published: March 2007

AbstractAutoantibodies reactive with nuclear envelope proteins are mainly detected in human sera from patients with liver diseases. Some of these antibodies are directed to lamin B, lamins A and C, or to the lamin B receptor (LBR). We show here that the latter one are anti‐idiotypic to certain anti‐lamin B antibodies. Using an enzyme‐linked immunosorbent assay specific for lamins we found that serum M containing anti‐LBR antibodies inhibited the binding to lamins of anti‐lamin B autoantibodies from three of five sera tested. Similar results were obtained using patient's M purified IgG. The binding of monoclonal IgM, λ anti‐lamin B antibodies produced by a lymphoblastoid cell line derived from the patient's blood lymphocytes was also inhibited. Absorption of serum M with nuclei abolished the inhibitory activity. No inhibition was recorded with normal sera or sera containing other antinuclear specificities. Anti‐LBR antibodies did not alter the binding to lamins of sera containing anti‐lamins A and C antibodies. Altogether these findings demonstrate that anti‐LBR antibodies are also combining site related anti‐idiotypic antibodies (Ab2) to certain anti‐lamin B antibodies, provide further evidence for discrete specificities among anti‐lamin B antibodies and suggest that the occurrence of autoantibodies to nuclear envelope antigens may be under idiotypic regulation.
Glucocorticoid‐dependent and ‐independent mechanisms involved in lipopolysaccharide tolerance
Authors: Evans Glenn F. , Zuckerman Steven H. 
Published: March 2007

AbstractInjection of bacterial lipopolysaccharide (LPS) into animals results in a transient increase in serum tumor necrosis factor (TNF). Maximal increases in TNF were detected by 1 h and by 3–4 h serum TNF was no longer apparent. These animals were LPS tolerant and a repetitive LPS stimulus did not result in an additional peak in TNF. Regulation of TNF expression in LPS‐tolerant animals was at the transcriptional level as TNF mRNA was not apparent in spleen or peritoneal macrophages following a second LPS stimulus. Adrenalectomized (adrex) mice, in contrast, did not become LPS tolerant and sera from these animals demonstrated an additional peak in TNF 1 h following a second LPS stimulus. Concomitant with the secondary rise in serum TNF in adrex mice was an increase in splenic TNF mRNA. The ability of adrex mice to become LPS tolerant was restored by exogenous glucocorticoids. LPS tolerance was also investigated in the galactosamine LPS model which like the adrex model is characterized by a thousandfold increase in the sensitivity of these animals to the lethal effects of LPS. Consistent with the absence of LPS tolerance in adrex mice, galactosamine‐sensitized mice were also responsive to a second LPS stimulus and did not become LPS tolerant. While LPS‐treated adrex mice had no significant increases in serum corticosterone, corticosterone levels in LPS‐treated galactosamine‐sensitized mice were comparable to LPS‐stimulated normals suggesting that LPS tolerance involves both glucocorticoid‐dependent and ‐independent components. Finally, prophylactic administration of a monoclonal antibody against murine TNF protected normal and galactosamine‐sensitized mice from a lethal dose of LPS and yet had no protective effect in adrex animals.
Antigen processing by endosomal proteases determines which sites of sperm‐whale myoglobin are eventually recognized by T cells
Authors: Van Noort Johannes M. , Boon Jacqueline , Van der Drift Alfons C. M. , Wagenaar Josée P. A. , Boots Annemieke M. H. , Boog Claire J. P. 
Published: March 2007

AbstractThis study reports an identification of the major processing products of an exogenous protein antigen, viz. sperm‐whale myoglobin, as obtained after cell‐free processing with partially purified macrophage endosomes. It is demonstrated that such a system yields fragments that are indistinguishable by high performance liquid chromatography analysis from those generated after uptake of myoglobin inside live macrophages.The concerted action of the endosomal proteases cathepsin D and cathepsin B can account for nearly all cleavages observed. Cathepsin D appears to be mainly responsible for the initial cleavage of myoglobin, while cathepsin B catalyzes the C‐terminal trimming of initially released fragments. The fragments released by cathepsin D contain most, if not all, major epitopes for murine myoglobin‐specific helper T cells.Interestingly, each known T cell epitope of myoglobin is located at the very N terminus of a different myoglobin fragment released upon processing. In order to explain this correspondence, noted also in several other protein antigens, a structural relationship is proposed between antigen processing by cathepsin D and antigen recognition by major histocompatibility complex (MHC) class II products. As is demonstrated here, this relationship may be used as a predictive tool for the identification of MHC‐binding sequences as well as of T cell epitopes in their naturally occurring form.