bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunodominance with progenitor B cell diversity in the neutralizing antibody repertoire to influenza infection
Authors: Patera Andriani C. , Graham Christine M. , Thomas D. Brian , Smith Claire A. 
Published: March 2007

AbstractWe report striking immunodominance in the neutralizing antibody responses of major histocompatibility complex congenic mice to natural infection with influenza virus (H3N2 subtype), as deduced by sequencing the hemagglutinin (HA) genes of monoclonal antibody (mAb)‐selected mutant viruses. A majority of mAb, established from individual BALB/c (H‐2d) mice, select mutant viruses containing the same single amino acid substitution in the membrane distal ectodomain, HA1 198 A→E, whereas changes at either HA1 158 G→E or HA1 198 A→E are selected for by mAb from BALB.K (H‐2k) donors. The structural basis for immunodominance, and potential diversity of progenitor B cells, was investigated by sequence analysis of H and L chain gene rearrangements in mAb specific for HA1 158 or HA1 198. No correlation was found between antibody specificity and VH or VL gene usage, and a minimum of three to six progenitor cells contributed to the individual's repertoire for a single antigenic site. However, in a further analysis of the HA1 158‐specific antibody response of CBA/Ca (H‐2k) donors, there was highly restricted light chain gene usage. Focusing of the immune repertoire to limited regions of the HA molecule during a primary viral infection may be a significant factor in immune pressure for antigenic variation, particularly since there is no evident restriction in the antibody response to immunization.
Distinct signaling properties identify functionally different CD4 epitopes
Authors: Baldari Cosima T. , Milia Elisabetta , di Somma M. Maddalena , Baldoni Fabiana , Valitutti Salvatore , Telford John L. 
Published: March 2007

AbstractThe CD4 coreceptor interacts with non‐polymorphic regions of major histocompatibility complex class II molecules on antigen‐presenting cells and contributes to T cell activation. We have investigated the effect of CD4 triggering on T cell activating signals in a lymphoma model using monoclonal antibodies (mAb) which recognize different CD4 epitopes. We demonstrate that CD4 triggering delivers signals capable of activating the NF‐AT transcription factor which is required for interleukin‐2 gene expression. Whereas different anti‐CD4 mAb or HIV‐1 gp120 could all trigger activation of the protein tyrosine kinases p561ck and p59fyn and phosphorylation of the Shc adaptor protein, which mediates signals to Ras, they differed significantly in their ability to activate NF‐AT. Lack of full activation of NF‐AT could be correlated to a dramatically reduced capacity to induce calcium flux and could be complemented with a calcium ionophore. The results identify functionally distinct epitopes on the CD4 coreceptor involved in activation of the Ras/protein kinase C and calcium pathways.
Characterization of critical residues in the cytoplasmic domain of the human interleukin‐5 receptor α chain required for growth signal transduction
Authors: Cornelis Sigrid , Fache Ina , van der Heyden José , Guisez Yves , Tavernier Jan , Devos René , Fiers Walter , Plaetinck Geert 
Published: March 2007

AbstractInterleukin (IL)‐5 binds to a cell surface receptor composed of two polypeptide chains, α and β, both belonging to the hemopoietic cytokine receptor family. Mouse cells expressing common mouse β chain (AIC2B) that were transfected with human IL‐5 receptor (R)α cDNA proliferated in response to picomolar concentrations of human IL‐5, indicating that a functional receptor was reconstituted. We show that in these cells, human (h)IL‐5 as well as mouse (m)IL‐3 induce tyrosine phosphorylation of β chain and JAK 2 kinase. Phosphorylated β receptor was co‐precipitated with anti‐JAK 2 antibodies, suggesting that both molecules were physically associated. IL‐5 and IL‐3 also induce cytosolic DNA binding activity as measured by an electrophoretic mobility shift assay using the interferon‐γ responsive region of human Fc γ1 gene DNA element. A deletion mutant of hIL‐5Rα lacking the cytoplasmic part could bind hIL‐5 normally in association with the β chain, but was unable to transmit a biological signal. The cytoplasmic domain was also indispensable for tyrosine phosphorylation and activation of DNA binding proteins. A membrane‐proximal proline‐rich element of the hIL‐5Rα cytoplasmic domain that is conserved among different members of the hemopoietic cytokine receptor family was essential for biological activity. Point mutations in this motif also knocked out IL‐5‐inducible JAK 2 phosphorylation.
CD20 monoclonal antibodies decrease interleukin‐4‐stimulated expression of the low‐affinity receptor for IgE (FcϵRII/CD23) in human B cells by increasing the extent of its cleavage
Authors: Bourget Isabelle , di Berardino Wilma , Breittmayer Jean‐Philippe , Grenier‐Brossette Nicole , Plana‐Prades Montserrat , Bonnefoy Jean‐Yves , Cousin Jean‐Louis 
Published: March 2007

AbstractCD20 monoclonal antibody (mAb) B1 is known to inhibit B cell proliferation. We show that B1 reduced both anti‐μ + interleukin‐4 (IL‐4)‐induced DNA synthesis and the concomitant expression of CD23 at the surface of human tonsillar B cells. B1 mAb had no effect on CD23 mRNA levels. The disappearance of CD23 molecule from the surface correlates with an increase of soluble CD23 fragments in the culture medium, indicating that CD20 mAb B1 stimulated the cleavage of the molecule. B1 also inhibits IgE production by peripheral blood mononuclear cells cultured in the presence of IL‐4. Suppression of IgE synthesis and enhancement of CD23 cleavage are concomitant but appear not to be functionally related.
Intra‐ and extra‐thymic expression of the pre‐T cell receptor α gene
Authors: Bruno Ludovica , Rocha Benedita , Rolink Antonius , von Boehmer Harald , Rodewald Hans‐Reimer 
Published: March 2007

AbstractWe have analyzed pre‐T cell receptor α (pTα) gene expression in cells from various anatomical sites to investigate the lineage specificity of pTα RNA as well as its presence in pro‐T cells and in sites of extrathymic T cell development. pTα RNA is found in precursors of αβ T cells but is absent from mature αβ T cells as well as T cells that express the γδ T cell receptor on the cell surface. pTα expression is exquisitely T lineage specific in that mature and immature B cells, myeloid cells, NK cells and pluripotent stem cells are pTα negative. On the other hand, pTα expression is found in pro‐T cells outside the thymus as well as in intra‐ and extra‐thymic sites of T cell development. The latter finding is consistent with the notion that early steps of T cell development within and outside the thymus may be similar.
Preferential recognition of specific DNA motifs by anti‐double‐stranded DNA autoantibodies
Authors: Herrmann Martin , Winkler Thomas H. , Fehr Holger , Kalden Joachim Robert 
Published: March 2007

AbstractAlthough antibodies (Ab) specific for double‐stranded (ds) DNA are thought to be involved in the etiopathogenesis of systemic lupus erythematosus (SLE), the fine structure of their DNA targets remains elusive. We have adapted a polymerase chain reaction (PCR)‐assisted immunoprecipitation method to define the binding sites in DNA sequences recognized by high affinity anti‐dsDNA Ab of SLE patients. SLE sera were used to bind templates from a pool of double‐stranded oligonucleotides (ON). A central part of 20 base‐pair random sequence was flanked by restriction endonuclease recognition sites and sequences complementary to predefined PCR primers. Immunoselected ON were precipitated, isolated from the immune complexes and then subjected to a further immunoprecipitation step after amplification by PCR. After five cycles of immunoprecipitation and PCR, the resulting ON were cloned. Sequence analysis revealed that sera from SLE patients and two human monoclonal anti‐dsDNA Ab obtained from SLE patients preferentially select sequences expected to form non‐B‐DNA structures. Inhibition studies of the Farr assay confirmed the increased affinity of the selected epitopes for anti‐DNA Ab as compared to random B‐DNA.
Prevention and treatment of Lewis rat experimental allergic encephalomyelitis with a monoclonal antibody to the T cell receptor Vβ8.2 segment
Authors: Imrich Horst , Kugler Christine , Torres‐Nagel Nora , Dörries Rüdiger , Hünig Thomas 
Published: March 2007

AbstractThe predominance of T cell receptor (TCR) Vβ8.2 utilization by encephalitogenic T cells induced in Lewis rats by immunization with myelin basic protein (MBP) is controversial. Thus, both an almost exclusive usage of Vβ8.2 [Burns, F. R., Li, X., Shen, N., Offner, H., Chou, Y. K., Vandenbark, A. A. and Heber‐Katz, E., J. Exp. Med. 1989. 169: 27; Chluba, J., Steeg, C., Becker, A., Wekerle, H. and Epplen, J. T., Eur. J. Immunol. 1989. 19: 279] and a quite diverse Vβ composition of CD4 T cells causing experimental autoimmune encephalomyelitis (EAE) [Sun, D., Gold, P. D., Smith, L., Brostoff, S. and Coleclough, C., Eur. J. Immunol. 1992. 22: 591; Sun, D., Le, J. and Coleclough, C., Eur. J. Immunol. 1993. 23: 494] have been reported. Using a recently developed monoclonal antibody (mAb) specific for TCR Vβ8.2, we show that postnatal treatment effectively eliminates Vβ8.2‐bearing cells and prevents MBP‐induced EAE in the majority of Lewis rats. Moreover, treatment of adult Lewis rats with Vβ8.2‐specific mAb as late as on day 12 after MBP immunization suppressed the development of neurological symptoms. Thus, Vβ8.2‐bearing cells do play a decisive role in Lewis rat EAE, and suppression of the small (5%) Vβ8.2‐expressing T cell subset provides an effective therapeutic strategy.
Self‐reactive anti‐class II T helper type 2 cell lines derived from gold salt‐injected rats trigger B cell polyclonal activation and transfer autoimmunity in CD8‐depleted normal syngeneic recipients
Authors: Saoudi Abdelhadi , Castedo Maria , Nochy Dominique , Mandet Chantal , Pasquier Régine , Druet Philippe , Pelletier Lucette 
Published: March 2007

AbstractBrown Norway (BN) rats given gold salts develop an autoimmune syndrome with an immune complex‐type glomerulonephritis in the context of a polyclonal B cell activation that was suspected to be due to the emergence of anti‐self major histocompatibility complex (MHC) class II T cells. In the present study, six anti‐self MHC class II T cell lines have been derived from six gold salttreated rats by repeated stimulations with normal syngeneic MHC class II‐bearing cells. The T cell lines proliferated in the presence of self MHC class II‐positive B cell‐enriched or B cell‐depleted cells and the proliferation was inhibited by preincubating stimulator cells with an anti‐IA monoclonal antibody. The T cell lines produced interleukin (IL)‐4 only or IL‐4 and some interferon (IFN)‐γ and could, therefore, be considered as T helper type 2 (Th2) and Th0 cells, respectively. They triggered normal syngeneic B cells to produce in vitro IgE, anti‐DNA, anti‐laminin and anti‐2,4‐6‐trinitrophenol antibodies through, at least in part, cognate interactions. More interestingly, these lines when transferred into normal BN rats induced an autoimmune syndrome similar to or even more severe than the one observed in the active gold model, provided the recipients were CD8 depleted. These manifestations included a dramatic increase in serum IgE concentration and the production of anti‐DNA and anti‐laminin antibodies. In addition, all recipients displayed an autoimmune glomerulonephritis due to anti‐laminin antibodies, granular IgG deposits in the interstitium, in the vessel walls and along the tubular basement membranes and a severe tubulointerstitial nephritis with marked mononuclear cell infiltration. An anti‐ovalbumin T cell line that produced IL‐4 and low amounts of IFN‐γ was used as a control and did not induce autoimmunity. These results demonstrate for the first time the ability of autoreactive Th2 as well as Th0 cell lines to induce antibody‐mediated autoimmunity. They also show that CD8+ cells play a crucial role in the control of such autoreactive cells. Finally, this work suggests that Th2 cells could initiate cell‐mediated reactions either directly or indirectly.
The role of lymphocyte subsets and adhesion molecules in T cell‐dependent cytotoxicity mediated by CD3 and CD28 bispecific monoclonal antibodies
Authors: Renner Christoph , Jung Wolfram , Sahin Ugur , van Lier Rene , Pfreundschuh Michael 
Published: March 2007

AbstractThe cure of human Hodgkin's tumors heterotransplanted into SCID mice can be achieved by two bispecific monoclonal antibodies (Bi‐mAb) directed against the tumor‐associated CD30 antigen and CD3 and CD28, respectively, and normal peripheral human blood T cells. We investigated the role of lymphocyte subsets and adhesion molecules in this Bi‐mAb‐mediated cytolysis. CD4+ lymphocytes were the most rapidly expanding subpopulation, but Bi‐mAb‐directed cytotoxicity was mediated preferentially by CD8+ lymphocytes and effector cells belonging to the CD45RO+ “memory” pool. Blocking of the LFA‐1/ICAM‐1 or CD2/LFA‐3 adhesion pathways by mAb decreased Bi‐mAb‐mediated cytotoxicity. This was not due to inhibition of aggregate formation between Bi‐mAb‐coated T lymphocytes and target cells. Cross‐linking of LFA‐1 or CD2 molecules on lymphocytes prestimulated with Bi‐mAb bound to CD3 and CD28 antigen lead to a more pronounced and prolonged rise in the intracellular concentration of free Ca2+. Additional CD2 cross‐linking resulted in the tyrosine phosphorylation of distinct proteins. These findings indicate that adhesion molecules play a critical role and function as co‐stimulatory signals rather than as cellular contact mediators in CD3 and CD28 Bi‐mAb‐stimulated T lymphocytes.
Spreading of the immune response to different myelin basic protein peptides in chronic experimental autoimmune encephalomyelitis in B10.RIII mice
Authors: Jansson Liselotte , Diener Per , Engström Åke , Olsson Tomas , Holmdahl Rikard 
Published: March 2007

AbstractB10.RIII mice develop chronic and relapsing experimental autoimmune encephalomyelitis (EAE) after immunization with the myelin basic protein (MBP) peptide 89‐101 (VHFFKNIVTPRTP). To investigate the basis for the chronicity of the disease, the subsequent development of an immune responses to other parts of the MBP protein were investigated. Onset of disease occurs 9‐25 days after immunization with MBP89‐101. T cell responses towards a series of MBP peptides were assessed in an enzyme‐linked immunospot assay detecting single cells secreting IFN‐γ. There were responses not only to MBP89‐101, but also towards peptides derived from sequences outside of MBP89‐101. These peptides were of two kinds: those with sequences completely outside the 89‐101 stretch of MBP; and those sharing a short sequence with MBP89‐101 depending on alternative splicing of MBP mRNA. Immunization with these peptides also produced chronic EAE and a spreading of the immune response to other MBP peptides. Immunization with stepped peptides around the relevant region (MBP87‐110) showed that peptides sharing a 6‐amino‐acid motif induced EAE after immunization. After MBP 89‐101 peptide immunization, T cells isolated from lymph nodes did not cross‐react in vitro to the other peptides sharing this motif. We suggest that one mechanism for the development of relapses during the disease course is the recruitment of new T cells with specificity for MBP peptides not derived from the peptide used for immunization. This is the first time such a mechanism has been demonstrated in a chronic autoimmune disease model.
Processing of a viral glycoprotein in the endoplasmic reticulum for class II presentation
Authors: Bartido Shirley M. , Diment Stephanie , Reiss Carol S. 
Published: March 2007

AbstractEndogenous processing of viral glycoproteins for presentation to CD4+ T cells is a poorly investigated aspect of antigen processing and presentation. This pathway may involve not only pathogens, but also self proteins, and may thus be involved in self‐tolerance. We have characterized the processing of the endoplasmic reticulum‐restricted glycoprotein (G) of vesicular stomatitis virus, termed poison tail (Gpt), biochemically and enzymatically, and by T cell recognition assays. Expressed with a vaccinia vector, Gpt remains endoglycosidase H‐sensitive and does not mature to endoglycosidase D sensitivity. The protein is degraded in the ER with a T1/2 of 4 h. Gpt peptides are not secreted since Gpt‐infected cells are unable to sensitize uninfected antigen‐presenting cells in an innocent bystander assay. Using flow cytometry, Gpt is undetectable on the plasma membrane; in contrast, wild‐type G is readily found on the surface or secreted into the milieu as soluble G following infection of A20 cells with a vaccinia recombinant expressing G. The degradation of Gpt is sensitive to the thiol reagent diamide and occurs optimally at physiological pH. A series of proteolytic inhibitors were tested: 3,4‐dichloroisocoumarin and 1‐chloro‐3‐tosylamido‐7‐amino‐2‐heptanone inhibited degradation, which suggests the involvement of a serine protease. The degradation does not require transport to the Golgi complex, and is not sensitive to a variety of lysosomotropic agents. We show that the degradation products include the immunogenic epitopes recognized by a panel of T cell clones and hybridomas.
Self‐reactive T cell clones in a restricted population of interleukin‐2 receptor β+ cells expressing intermediate levels of the T cell receptor in the liver and other immune organs
Authors: Kawachi Yasuyuki , Watanabe Hisami , Moroda Tetsuya , Haga Manabu , Liai Tsuneo , Hatakeyama Katsuyoshi , Abo Toru 
Published: March 2007

AbstractT cells expressing high levels of the T cell receptor (TCRhigh) differentiate in the major intrathymic pathway and then distribute to the peripheral immune organs, whereas T cells expressing intermediate levels of the TCR (TCRint) differentiate in both extrathymic pathways and an alternative intrathymic pathway and localize in unique sites, including the liver and thymic medulla. Since TCRint cells constitutively express interleukin‐2 receptor β‐chain (IL‐2R), two‐color staining for CD3 (or TCR) and IL‐2Rβ clearly distinguished IL‐2RßT+ CD3int (or TCRint) cells from IL‐2Rβ−, CD3high cells. CD3int cells may be considered to be primordial T cells based on their phenotype, morphology and other functional properties. In this study, using anti‐Vβ mAb in conjunction with the endogenous superantigen Mls, the distribution of self‐reactive clones among T cells generated in all of the above pathways was investigated in mice. Self‐reactive T cell clones were confined to IL‐2Rβ+, CDint cells, in all of the organs tested. A significant proportion of self‐reactive clones was never identified among CD3high cells in the thymus and peripheral immune organs in either young (8 week old) or old (50 week old) mice. Possibly reflecting their self‐reactivity, CD3int cells, but neither NK cells nor CD3high cells had a potent cytotoxic effect against a syngeneic hepatoma in the presence of anti‐CD3 mAb. These results raise the possibility that CD3int cells seen in the liver and thymus might belong to a similar primordial lineage of T cells, and that self‐reactive clones are not generated through the major intrathymic pathway, but only through extrathymic pathways and an alternative intrathymic pathway.
Tumor cells cotransfected with interleukin‐7 and B7.1 genes induce CD25 and CD28 on tumor‐infiltrating T lymphocytes and are strong vaccines
Authors: Cayeux Sophie , Beck Christian , Aicher Alexandra , Dörken Bernd , Blankenstein Thomas 
Published: March 2007

AbstractInterleukin‐7 (IL‐7) and the membrane molecule B7 are both able to provide proliferation and activation signals for T cells. However, tumor cells transfected to express either molecule alone are not reliably rejected in syngeneic hosts or are not sufficiently immunogenic to serve as potent tumor vaccines. Since IL‐7 and B7 have shown synergistically to induce activation and proliferation of T cells in vitro, we have expressed B7.1 by means of a retrovirus in the mammary adenocarcinoma TS/A which arose spontaneously in a BALB/c mouse and in the plasmacytoma J558L and their IL‐7‐transfected sublines to improve vaccine efficacy. Expression of IL‐7 or B7.1 alone in tumor cells decreased tumorigenicity, but nevertheless tumors grew in a substantial number of mice. In contrast, IL‐7/B7.1 cotransfected cells did not grow as tumor in a single case. This inhibition of tumor growth was completely T cell dependent, because TS/A‐IL‐7/B7.1 cells retained their full tumorigenic potential in T cell‐deficient mice. Analysis of tumor‐infiltrating T lymphocytes revealed increased numbers of T cells in B7, IL‐7 and IL‐7/B7 transfected compared to parental tumors. In IL‐7/B7 transfected tumors, T cell numbers were not further increased compared to that in singlegene‐transfected tumors. However, T cells in B7 and IL‐7 transfected tumors differed phenotypically with respect to activation markers. In B7 transfected tumors, T cells were predominantly CD28+ and CD25+, while in IL‐7‐transfected tumors, T cells were mainly CD28− and CD25+. In IL‐7/B7 cotransfected tumors, the majority of T cells was CD28+ and CD25+. Thus, IL‐7 and B7 induced an anti‐tumor immune response by complementary T cell directed pathways in a cooperative fashion. Importantly, immunization of mice with the transfected cells and subsequent contralateral challenge with parental tumor cells showed that IL‐7/B7 co‐expressing cells induced the most strongly protective immunity, which is superior to that induced by single‐gene transfectants and to the adjuvant Corynebacterium parvum. Vaccine efficacy was abrogated when irradiated cells were used for vaccination. Together, our results show that IL‐7 and B7.1 transfected tumor cells induce strong T cell activation and tumor immunity.
A CD44 monoclonal antibody differentially regulates CD11a/CD18 binding to intercellular adhesion molecules CD54, CD102 and CD50
Authors: Vermot‐Desroches Claudine , Wijdenes John , Valmu Leena , Roy Catherine , Pigott Rod , Nortamo Pekka , Gahmberg Carl G. 
Published: March 2007

AbstractWe have made a monoclonal anti‐CD44 antibody which is able to activate the leukocyte integrin CD11a/CD18. Activated T cells strongly aggregated, and the aggregation was shown to be intercellular adhesion molecule (ICAM)‐1 (CD54) and ICAM‐2 (CD102) dependent. Using purified ICAM coated on plastic, only binding to ICAM‐1 was increased by the CD44 antibody, whereas activation by phorbol ester increased binding to both ICAM‐1 and ICAM‐3. The binding to ICAM‐2 was not affected by either treatment. These findings show that the CD11a/CD18 integrin can be activated in a ligand‐specific manner by engagement of CD44.