bluuebunny/crossref_metadata_2025_split huggingface dataset:
Graft rejection by T cells not restricted by conventional major histocompatibility complex molecules
Authors: Dierich Andrée , Chan Susan H. , Benoist Christophe , Mathis Diane 
Published: March 2007

AbstractThe appropriate crosses of mice lacking conventional major histocompatibility complex (MHC) class I or class II molecules generate single‐ and double‐deficient offspring. These were used as donors for skin grafts across major plus minor, or just minor, histocompatibility differences. Surprisingly, in the two circumstances, there was a rapid rejection of grafts lacking both MHC class I and class II molecules. Rejection was mediated by thymically derived CD4+ T cells of the host. We provide evidence that these T cells recognize an unconventional ligand, capable of activating a pre‐formed T cell compartment but incapable of positively selecting it. The existence of this unexpected rejection phenomenon should serve to caution those aiming to engineer “universal donor” cells by simply abrogating expression of MHC class I and class II molecules.
Contrasting efficacy of presentation by major histocompatibility complex class I and class II products when peptides are administered within a common protein carrier, self immunoglobulin
Authors: Zaghouani Habib , Kuzu Yukiko , Kuzu Hiroshi , Brumeanu Teodor D. , Swiggard William J. , Steinman Ralph M. , Bona Constantin A. 
Published: March 2007

AbstractMajor histocompatibility complex (MHC) class I and II products are specialized to present antigens via different intracellular processing routes. Peptides originating from proteins in the cytoplasm can gain access to class I peptide‐binding grooves, most likely in the rough endoplasmic reticulum. Peptides from proteins in acidic endocytic vacuoles gain access to class II. It has been proposed that MHC class I products also can capture peptides from “exogenous” or noninfectious sources, and this assumption underlies the use of intact proteins as vaccines for CD8+ cytotoxic T lymphocytes. Here we describe quantitative information comparing the efficacy of peptide presentation from exogenous proteins by administering a class I‐ and II‐restricted peptide within the same context, the CDR3 loop of the VH domain of a self immunoglobulin. Antigen‐presenting cells (APC), including primary dendritic cells, efficiently present an influenza hemagglutinin peptide from the immunoglobulin (Ig) carrier (50% maximal response at 10 nM Ig‐HA) to an MHC class II‐restricted T cell. In contrast, these same APC are unable to present an influenza nucleoprotein (NP) peptide from the same context (1 μM Ig‐NP) to an MHC class I‐restricted T cell. Ig‐NP DNA transfectants do present the nucleoprotein viral peptide on class I. Thus, peptides within the complementarity‐determining region loops of Ig carriers can be presented on class I or II MHC products, but the endocytic compartment, when offered MHC class I‐ and II‐restricted peptides within the same carrier protein context, favors presentation by class II by at least 1000‐fold.
Identification of an endogenous mammary tumor virus involved in the clonal deletion of Vβ2 T cells
Authors: Jouvin‐Marche Evelyne , Marche Patrice N. , Six Adrien , Liebe‐Gris Carine , Voegtle Danielle , Cazenave Pierre‐André 
Published: March 2007

AbstractExpression of Vβ (β ‐chain variable region) gene segments was investigated in the Mus m. domesticus DDO strain, which possesses a large genomic deletion encompassing 20 of the 29 Vβ gene segments known in BALB/c. Stainings using Vβ ‐specific monoclonal antibodies revealed that up to 60% of the peripheral T cells use 3 Vβ gene segments. Variable frequencies of Vβ 2 T cells were observed among DDO individuals. Segregation analyses of F2 crosses between Vβ 2‐deletor mice and mammary tumor virus (Mtv)‐free mice led to the identification of a new endogenous Mtv, named Mtv‐DDO, mediating Vβ 2 Tcell clonal deletion. Mtv‐DDO structure is conserved with the exception of the carboxy‐terminal region as compared to other Mtv. Comparison between Mtv sharing the same Vβ specificity and isolated from laboratory or wild mice confirms that a stretch of 11 amino acids, defined as the Vβ ‐specific region, is required for the Vβ ‐specific interaction. Limited substitutions in this region account for the shift of the Mtv specificity towards different Vβ.
A new infectious mammary tumor virus in the milk of mice implanted with C4 hyperplastic alveolar nodules
Authors: Shakhov Alexander N. , Wang Hong , Acha‐Orbea Hans , Pauley Robert J. , Wei Wei‐Zen 
Published: March 2007

AbstractWe have previously characterized an infectious mouse mammary tumor virus [(MMTV(SW)] which induces a strong superantigen response in vivo. Here we describe the isolation and characterization of MMTV(C4) which was derived from milk of mice implanted with hyperplastic alveolar nodules. MMTV(C4) stimulates Vβ2 expressing T cells after local injection in vivo. Comparison with known open reading frame (orf) sequences revealed high homology to Mtv‐6, an endogenous virus interacting with Vβ3‐expressing T cells. The carboxyl‐terminal amino acids were, however, altered. High homology including the carboxyl‐terminal orf amino acids were found with MMTV(C3H‐K). We show here that MMTV(C3H‐K) has lost its superantigen function. Sequence comparisons permitted the characterization of few key amino acids which could be important for T cell receptor interaction and superantigen processing.
Tumors with reduced expression of a cytotoxic T lymphocyte recognized antigen lack immunogenicity but retain sensitivity to lysis by cytotoxic T lymphocytes
Authors: Koeppen Hartmut , Acena Maria , Drolet Aimee , Rowley Donald A. , Schreiber Hans 
Published: March 2007

AbstractA murine solid tumor was transfected to express various levels of an allogeneic major histocompatibility complex class I gene (K216), in order to test the effect of the level of antigen expression on immunogenicity and sensitivity to lysis by cytotoxic T lymphocytes (CTL). The growth rates of clones of tumor cells expressing different levels of the transfected gene were similar in vitro and in nude mice. Although all tumor cells, including cells freshly isolated from growing tumors, were equally sensitive to lysis by specific CTL, only tumor cells expressing the highest level of the K216 antigen stimulated CTL and were rejected by normal mice. In contrast, tumor cells expressing lower levels of antigen failed to immunize for CTL and grew progressively in normal mice, despite retaining expression of the transfected gene and remaining fully sensitive to CTL‐mediated lysis; thus, the threshold of antigen needed to stimulate CTL responses was considerably higher than that needed to lyse tumor cells. Reduction of K216 antigen expression from 100‐fold to 40‐fold above background, impaired significantly the ability of the tumor cells to induce a K216‐specific immune response, while tumor cells expressing K216 at levels 2‐fold above background were as susceptible to CTL‐mediated lysis as tumor cells expressing 50‐fold more antigen. The important implication of these findings is that some tumors occurring in nature may not be immunogenic but nevertheless express antigens which are potential targets for immune therapy.
Activation of human monocytes and granulocytes by monoclonal antibodies to glycosylphosphatidelinositol‐anchored antigens
Authors: Lund‐Johansen Fridtjof , Olweus Johanna , Symington Frank W. , Arrli Aanen , Thompson John S. , Vilella Ramon , Skubitz Keith , Horejsi Vaclav 
Published: March 2007

AbstractThe present study investigated possible receptor‐like characteristics of glycosyl‐phosphatidylinositol (GPI)‐linked antigens on human monocytes and granulocytes by measuring cytoplasmic calcium fluxes and the oxidative burst in cells following cross‐linking of GPI‐linked antigens. Cross‐linking of cell‐bound anti‐CD14, ‐CDw52 and ‐CD55 induced cytoplasmic calcium fluxes and oxidative bursts in unprimed human monocytes similar to those observed following FcyR cross‐linking. In granulocytes primed with 200 nM N‐formyl‐Met‐Leu‐Phe (FMLP), cross‐linking of cell‐bound anti‐CD16, ‐CD24, ‐CD59 and ‐CD67 led to calcium fluxes and activation of the oxidative burst. The oxidative bursts mediated by GPI‐linked antigens were stronger than those induced by 200 nM FMLP, even though FMLP induced a larger increase in cytoplasmic calcium concentration. The responses were likely to be independent of FcyR interactions as F(ab′)2 fragments of IgG or IgM antibodies were used in the experiments. Activating effects of monoclonal antibody to GPI‐linked antigens were not observed in cells from patients with paroxysmal nocturnal hemoglobinuria, which are deficient in GPI‐linked antigens. In addition, treatment with GPI‐specific phospholipase C led to inhibition of cell activation through GPI‐linked antigens but not through transmembrane receptors. Cross‐linking of a number of non‐GPI‐linked antigens (CD11a, CD18, CD31, CD35, CD43, and CD45) neither induced calcium fluxes, nor activated the oxidative burst. The results indicate that most, if not all, GPI‐linked surface glycoproteins on myeloid cells are capable of mediating cell activation and suggest that the GPI anchor is a structure facilitating signal transduction.
Somatic diversification and affinity maturation of IgM and IgG anti‐DNA antibodies in murine lupus
Authors: Hirose Sachiko , Wakiya Midori , Kawano‐Nishi Yasuko , Yi Jiang , Sanokawa Reiko , Taki Shinsuke , Shimamura Toshiroh , Kishimoto Toshihiko , Tsurui Hiromichi , Nishimura Hiroyuki , Shirai Toshikazu 
Published: March 2007

AbstractMolecular events occurring during the process of generation of pathogenic immunoglobulin (Ig)G anti‐DNA antibodies in systemic lupus erythematosus (SLE) were studied using a newly established method. We analyzed the Ig variable (V) region gene sequence and DNA‐binding activity of IgM and IgG anti‐DNA monoclonal antibodies (mAb) from individual SLE‐prone (NZB × NZW) F1 mice. The first event appeared to be clonal selection and expansion of IgM anti‐DNA clones, in which several clones had intraclonal V gene mutations. Although the number of mutations was small, the mutated IgM clones were associated with an increase in DNA‐binding activity. The somatic mutations located in complementarity‐determining regions (CDR) and in framework regions (FR) of V genes were apparently related to changes in DNA‐binding activity. IgG anti‐DNA clones that progressively increased in number with aging had numerous somatic mutations in the V region genes and there was a pair of clones which showed an intraclonal accumulation of mutations, in association with increase in the DNA‐binding activity. All these findings show that somatic mutations associated with affinity maturation of the V region begin immediately before isotype‐switching from IgM to IgG of the clones that have been selected and expanded, in an antigen‐driven manner and/or by other forces. We propose that further accumulations of intraclonal somatic hypermutation, in association with selection and expansion of high affinity IgG clones, may lead to formation of highly pathogenic anti‐DNA antibodies.
The lack of CD8α cytoplasmic domain resulted in a dramatic decrease in efficiency in thymic maturation but only a moderate reduction in cytotoxic function of CD8+ T lymphocytes
Authors: Fung‐Leung Wai‐Ping , Louie Marjorie C. , Limmer Andreas , Ohashi Pamela S. , Ngo Karen , Chen Lei , Kawai Kazuhiro , Lacy Elizabeth , Loh Dennis Y. , Mak Tak W. 
Published: March 2007

AbstractThe glycoprotein CD8 is believed to play an important role in the maturation and function of MHC class I‐restricted T lymphocytes. CD8 has been proposed to function as a co‐receptor of the TcR to participate in signal transduction, possibly through its cytoplasmic domain that binds to protein tyrosine kinase p56lck. A T cell‐specific transgene encoding CD8α truncated at the cytoplasmic domain (“tailless CD8α”), was introduced into CD8α‐deficient mice. This animal model was used to study the role of the CD8 cytoplasmic domain in T cell ontogeny and function. “Tailless CD8α” was expressed on the cell surface of thymocytes and peripheral T cells. A small population of peripheral CD4− T cells (6% of T lymphocytes) was found to have cell surface expression of “tailless CD8α” and endogenous CD8β indicating that these cells may belong to the CD8+ T cell lineage. A consistent result was obtained from CD8α‐deficient mice bearing the “tailless CD8α” and the MHC class I‐restricted 2C TcR transgenes. A small population of CD4 T cells expressing CD8β the “tailless CD8α” and the 2C TcR transgenes was present in the periphery of these mice in a selecting background, but was absent in a deleting background. When “tailless CD8α” mice were infected with lymphocytic choriomeningitis virus (LCMV), the peripheral CD8+ CD4− T cell subset expanded dramatically and a significant LCMV‐specific cytolytic activity was detected. The results suggest that the cytoplasmic portion of CD8α is not absolutely required but dramatically enhances the eficiency of thymic maturation of CD8+ T cells. The lack of CD8α cytoplasmic domain in peripheral CD8+ T cells does not abolish the generation of cytotoxicity in response to an in vivo LCMV infection, although the cytolytic activity is slightly reduced compared to that in control mice.
The Vχ genes of the L regions and the repertoire of Vχ gene sequences in the human germ line
Authors: Huber Christian , Schäble Karlheinz F. , Huber Erwin , Klein Ralph , Meindl Alfons , Thiebe Rainer , Lamm Rosemarie , Zachau Hans G. 
Published: March 2007

AbstractOnly 14 of the 25 Vχ genes and pseudogenes had been found before as parts of the L regions. The cloning and linking described in the accompanying report allowed us now to assign to Lp or Ld some Vχ genes which had been found before on scattered clones. In addition the sequences of several still unknown genes are reported here, thus completing the publication of the Vχ genes of the x locus as far as they are potentially functional or have only one or two 1‐bp defects. Of the Vχ genes of the K locus, 32 are potentially functional, 16 have minor defects, 3 have both potentially functional and slightly defective alleles and 25 are pseudogenes which amounts to a repertoire of 76 Vχ‐related gene sequences. The Vχ genes of the L regions are, within the subgroups, particularly similar to each other, which is in part due to common evolutionary origins and in part caused by gene conversion‐like events. One donor‐acceptor pair could be clearly identified, since converted and not‐converted alleles of the acceptor gene were found. In other cases the duplicates of the converted genes served as non‐converted controls.
Antisense oligonucleotides specific for regulatory factor RFX‐1 inhibit inducible but not constitutive expression of all major histocompatibility complex class II genes
Authors: Siegrist Claire‐Anne , Mach Bernard 
Published: March 2007

AbstractThe regulation of major histocompatibility complex (MHC) class II genes expression, which can be constitutive, inducible or both, is a crucial aspect of the control of an immune response. It involves binding of various regulatory factors to cis‐acting sequences of MHC class II promoters. Antisense oligonucleotides specific for RFX‐1, a regulatory factor binding to the functionally essential X box motive of MHC class II promoters, were designed to study the role of RFX‐1 in the various modes of MHC class II regulation and explore the possibility of experimentally modulating the level of expression of MHC class II genes by transcriptional intervention. RFX‐1 antisense oligonucleotides were first tested in cell‐free translation, selected for an inhibitory effect on RFX‐1 in vitro translation and then assayed in cell cultures for an effect on human histocompatibility leukocyte antigen (HLA) class II expression. We show that an RFX‐1 specific antisense oligonucleotide drastically inhibits induction of HLA‐DR, ‐DQ and ‐DP molecules by interferon γ in monocytic cells. Unexpectedly, the same agent has no effect on the constitutive expression of the same genes either in these cells or in B lymphocytes, indicating an uncoupling of the constitutive and inducible modes of class II regulation. This transient and reversible experimental modulation of MHC class II expression in live cells by transcriptional intervention provides a new tool to study the function of class II molecules in various biological models.
Production and characterization of two murine monoclonal antibodies directed against epitopes exclusive to soluble fragments of FcεRII/CD23
Authors: Ghaderi Abbas A. , Stanworth Denis R. 
Published: March 2007

AbstractTwo murine monoclonal antibodies (mAb) designated as SU1 and SU3 directed against soluble FcεRII/CD23 have been generated by fusing X.63.AG.8653 (a mouse myeloma cell line) with spleen cells from mice immunized with an Epstein Barr virus (EBV)‐transformed B cell line (RPMI‐8866). The antibodies have been shown to be capable of detecting affinity purified soluble FcεRII/CD23 in an enzyme‐linked immunosorbent assay. Indirect immunofluorescence has shown that the SU1 and SU3 mAb do not stain RPMI‐8866, a FcεRII/CD23+ B cell line. By studying the migration profiles of affinity purified SU1‐ and SU3‐reactive molecules on sodium dodecylsulfate‐polyacrylamide gel electrophoresis it has been shown that SU1 mAb immunoprecipitates 33‐ and 12‐kDa components, while the SU3 mAb recognized 25‐ and 45‐kDa proteins from culture supernatants of RPMI‐8866 cells. Moreover, affinity purified SU1‐ and SU3‐reactive proteins have been shown to be recognized by human IgE but not by the human IgG molecule. These results provide evidence that SU1 and SU3 mAb may recognize some putative post‐cleavage epitopes on the N‐terminal end of the low affinity receptor which appear, perhaps, following the process of fragmentation. In addition, the effect of these antibodies on continuous growth of a panel of lymphoblastoid cell lines indicates that SU1 mAb was found incapable of influencing the spontaneous proliferation of EBV‐immortalized B cell lines; whereas SU3 mAb completely blocked the spontaneous growth and proliferation of all B cell lines tested. The results are discussed in relation to the appearance of a functional post‐cleavage epitope on soluble FcεRII/CD23.
Effects of murine leukemia viruses on the function of dendritic cells
Authors: Gabrilovich Dmitry I. , Roberts Mary S. , Harvey Jennifer J. , Botcherby Marc , Bedford Penelope A. , Knight Stella C. 
Published: March 2007

AbstractIn asymptomatic human immunodeficiency virus‐1 infection T cells respond normally to allogeneic dendritic cells (DC), but DC show reduced stimulatory capacity. By contrast in HTLV‐1 infection no significant changes in allogeneic stimulation were seen but DC‐stimulated activity of autologous T cells. In seeking animal models relevant to these diseases the effects of two murine leukemia retroviruses, Rauscher leukemia virus (RLV) and Moloney leukemia virus (MLV) on the function of dendritic cells and T cells in a primary mixed leucocyte reaction have been tested. Treatment by RLV in vitro suppressed the ability of DC to stimulate allogeneic T cells from healthy animals. MLV at the same concentration did not significantly affect the ability of DC to stimulate allogeneic T cells, but provoked considerable enhancement of the low level stimulation by DC in the syngeneic system. Similar results were obtained following in vivo exposure to viruses. Two pieces of evidence suggested that these effects were due to impairment of DC function and were not operating through infection of T cells. Firstly, exposure of T cells directly to virus in vitro and in vivo before stimulation with untreated allogeneic DC caused no significant alteration in T cell activity. Secondly, the impact of murine leukemia virus on DC function was not abrogated when infected DC were added to normal T cells and cultured in the presence of zidovudine. Treatment of DC by RLV caused a decrease of cluster formation with allogeneic T cells. No statistically significant influence of MLV was observed on cluster formation after 3‐h of incubation in the allogeneic system. However, after 18‐h incubation MLV‐treated DC formed fewer clusters with T cells than untreated DC. At the same time a stimulatory effect of MLV on DC cluster formation with syngeneic T cells was found. Considerable decrease was found in major histocompatibility complex class II antigen and LFA‐1 receptor expression on the DC surface in mice infected by RLV MLV induced no significant changes. These mouse retroviruses can therefore cause changes in DC function similar to those already reported using human retroviruses and may provide models for studying their effects.
Cleavage and inactivation of human C1 inhibitor by the human leukocyte proteinase, proteinase 3
Authors: Leid R. Wes , Ballieux Bart E. P. B. , van der Heijden Ineke , Kleyburg‐van der Keur Carin , Hagen E. Christiaan , van Es Leendert A. , van der Woude Fokko J. , Daha Mohamed R. 
Published: March 2007

AbstractIncubation of highly purified human C1 inhibitor with equally pure human leukocyte proteinase 3, resulted in a dose‐ and time‐dependent inactivation of C1 inhibitor hemolytic activity. Furthermore, this inactivation was accompanied by proteinase 3‐dependent cleavage of the C1 inhibitor into an 83 000 molecular weight fragment. The formation of the 83 000 molecular weight fragment followed a time course which was similar to that observed for the inactivation of hemolytic activity. Within 120 minutes more than 90% of the hemolytic activity was lost. This inactivation of C1 inhibitor appeared to be selective as purified human Clq was not degraded in a similar time period. Moreover, when 100 μg IgG, isolated from each of 21 Wegener's granulomatosis patients with cytoplasmic anti‐nuclear antibodies immunofluoresent titers to proteinase 3 greater then 1:64, was incubated with 3 milliunits of proteinase 3, little to no cleavage of C1 inhibitor was observed. In contrast, 100 μg of IgG isolated from 14 normal donors was ineffective in affording protection to C1 inhibitor upon incubation with proteinase 3. Our results suggest that neutrophil infiltration and activation could lead to local complement consumption at the tissue sites.
Selection of the expressed B cell repertoire by infusion of normal immunoglobulin G in a patient with autoimmune thyroiditis
Authors: Dietrich Gilles , Varela Francisco J. , Hurez Vincent , Bouanani Majida , Kazatchkine Michel D. 
Published: March 2007

AbstractIn the present study we have analyzed the changes in the expressed antibody repertoire and in temporal fluctuations of antibody levels in serum that followed infusion of normal IgG (IVIg) in a patient with autoimmune thyroiditis. Administration of IVIg resulted in the stimulation of IgM production, in alterations of expressed antibody activity in serum that could not merely be accounted for by the passive transfer of antibody specificities contained in IVIg, in transient down‐regulation of B cells clones expressing a specific disease‐related idiotype and in the increase in serum in recipient's autoantibodies specifically reactive with F(ab′)2 fragments of IVIg. In addition, infusion of IVIg shifted the pattern of spontaneous fluctuations of autoantibody activities in the patient's serum from a pattern indicative of disconnected events in the immune network to a pattern similar to that which is consistently observed in healthy controls. These results suggest that normal IgG may modulate autoreactivity by selecting expressed antibody repertoire through V region‐dependent interactions with antibodies.