bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antigen presentation of myoglobin: profiles of T cell proliferative responses following priming with synthetic overlapping peptides encompassing the entire molecule
Authors: Bider Garvin S. , Atassi M. Zouhair 
Published: February 2007

AbstractRecently, the regions of myoglobin, which are recognized by T cells (T sites), were localized by a comprehensive synthetic strategy in which uniform synthetic overlapping peptides encompassing the entire protein chain were examined for stimulation of T cell proliferative activity. In this study, we report about the proliferative response to these peptides, as well as to the native protein, of lymph node cells from mice primed with the overlapping peptides either individually or in a mixture. Some, but not all, of the T site‐containing peptides were effective in priming for an anti‐myoglobin T cell response. Further, several peptides, which were highly immunogenic as free synthetic peptides, were not associated with any of the known T sites in this protein. Thus, the pattern of T cell recognition following priming with the overlapping peptides differs from the pattern observed when the native protein is the priming antigen. If antigen processing proceeds via fragmentation, then only those regions containing T sites would be expected to be effective in priming for a T cell response to the intact protein and, conversely, highly immunogenic peptides would correspond to T sites of the protein. Therefore, these findings indicate that the current concept of antigen fragmentation as a prerequisite for its presentation must be reappraised. We suggest that, in the presentation of a protein antigen, the protein is recognized predominantly intact and that the crucial aspects of presentation are determined by interaction with the cell membrane which trigger cellular activating events.
Analysis of the Thy‐1 pathway of T cell hybridoma activation using 17 rat monoclonal antibodies reactive with distinct Thy‐1 epitopes
Authors: Pont Suzanne , Regnier‐Vigouroux Anne , Naquet Philippe , Blanc Dominique , Pierres Anne , Marchetto Sylvie , Pierres Michel 
Published: February 2007

AbstractSeventeen monoclonal anti‐Thy‐1 antibodies (mAb) derived from LOU/M rats immunized with mouse T cell clones were used to study the role of Thy‐1 in antigen‐independent T cell activation. These mAb identified Thy‐1.2 or monomorphic determinants and immunoprecipitated a molecule of 25–28 kDa from detergent‐sol‐ ubilized, 125I‐labeled T cell surface proteins. Competitive cross‐inhibition binding assays demonstrated that these reagents defined 3 epitope groups including either Thy‐1.2 (group A) or Thy‐1 monomorphic (groups B and C) determinants. Experiments using high titered culture supernatants revealed that all 6 IgG mAb defining the epitope group C, and one IgG2c mAb directed at a determinant in group A were capable of stimulating the terpolymer‐L‐glutamic acid60‐L‐alanine33‐Ltyrosine10(GAT) plus I‐Ad‐reactive BALB/c T cell hybridoma T14–117.9 to produce inter‐leukin 2 (IL2) in the absence of accessory cells. Cross‐linking of cell‐bound rat mAb by a BALB/c anti‐rat kappa chain mAb, or the presence of B cell lymphomas in the culture resulted in an increase of the Thy‐1‐mediated IL2 responses of this hybridoma. Some mAb from group B required antibody doses exceeding 80 üg/ml in order to activate T cells, while others remained nonstimulatory at any dose tested. Striking synergy in rnAb‐mediated T cell activation was observed when nonmitogenic doses of mAb group groups A and C were mixed in the same culture. Analysis of a panel of GAT plus I‐Ad‐specific T cell hybridomas revealed that these cells markedly differed in the magnitude of their IL2 responses induced by a given amount of stimulating anti‐Thy‐1 mAb. Such reagents also stimulated normal thymocytes to express IL2 receptor on their surface. These studies show that the epitopic specificity and the amount of anti‐Thy‐1 mAb, and the susceptibility of the T cell examined represent important parameters for the triggering of the Thy‐1 pathway of T cell activation.
T cells specific for different antigens express different HLA‐D region products
Authors: Schendel Dolores J. , Johnson Judith P. 
Published: February 2007

AbstractT cell lines and clones were analyzed for surface expression of la antigens using monoclonal antibodies (mAb) that detect monomorphic and polymorphic epitopes on la molecules encoded by the HLA‐DR and HLA‐DQ gene clusters. All mAb bound to B lymphocytes or lymphoblastoid cell lines of the same individuals from whom the T cells were derived. Three mAb detecting monomorphic epitopes, primarily associated with HLA‐DR, bound to all T cells showing that each clone or line expressed some type of la. Three other mAb defining polymorphic epitopes associated with HLA‐DR products showed differential binding patterns. Two reagents, R3 and E15/4 recognizing the supertypic specificity DRw52 (formerly MT2), bound to every alloreactive clone, whereas the 16.23 mAb, detecting a private DR3‐associated epitope, failed to bind to any clone. In contrast, the 16.23 epitope was detected on high percentages of T cells specific for purified protein derivative of tuberculin (PPD) or tetanus toxoid (TT). Biochemical studies showed that the 16.23 and DRw52‐like epitopes can be present on distinct DR molecules on B cell lines and this may also be the case for T cells.Three other mAb, detecting epitopes associated with HLA‐DQ, also revealed differential binding patterns when tested on various T cells. Two failed to bind to any alloreactive clone and to only low numbers of PPD‐ or TT‐specific T cell lines, whereas the third bound distinctly to a CD4+/CD8+ alloreactive clone. Biochemical analyses have shown that these DQ epitopes can be present on different molecules. Combined, these observations indicate that differential expression of la molecules encoded by both HLA‐DR and DQ occurs between B and activated T cells as well as among T cell populations of the same individual. Whether these differences reflect quantitative variations in expression of given DR or DQ molecules or, alternatively, are due to differential class II gene expression in activated T cells remains to be determined.
Eosinophil activation by lymphokines and T cell clone products in the rat
Authors: Veith Monica , Pestel Jöel , Loiseau Sylvie , Capron Monique , Capron André 
Published: February 2007

AbstractT cell lines and T cell clones derived from inbred Fischer rats and specific for Schistosoma mansoni antigens were established. Cell‐free supernatants from the T cell lines demonstrated a marked capacity to enhance IgE‐ and IgGa‐dependent eosinophil mediated killing of S. mansoni larvae in vitro. In addition, supernatants from cloned T cells stimulated with concanavalin A or specific antigen, or unstimulated, enhanced IgE‐dependent eosinophil‐mediated helminthotoxicity. The enhancing activity in both cases was very heat‐stable (100°C, 10 min). We also found that clone‐derived supernatants enhance eosinophil peroxidase release upon stimulation with homologous IgE and anti‐IgE as well as inducing a more delayed spontaneous release of peroxidase. In view of the established thymus dependency for the development of immunity to schistosomiasis in the rat, the availability of these s. mansoni‐specific cloned T cells has enabled the relationship between eosinophils, lymphocytes and anaphylactic antibodies to be examined more closely.
Analysis of lysozyme‐specific immune responses by synthetic peptides. I. Characterization of antibody and T cell‐mediated responses to the N‐terminal peptide of hen egg‐white lysozyme
Authors: Sette Alessandro , Colizzi Vittorio , Appella Ettore , Doria Gino , Adorini Luciano 
Published: February 2007

AbstractThe immunological reactivity against the N‐terminal region of hen egg‐white lysozyme (HEL) has been investigated by a synthetic peptide (PHEL) comprising residue 1–18 of HEL and by an analogue peptide (PREL) in which phenylalanine at position 3 is substituted by tyrosine. Both peptides are immunogenic in (C57BL/10 × DBA/2)F1 mice genetically responder to HEL. In C57BL/6 mice, genetically nonresponder to HEL, PREL induces anti‐peptide antibodies that also bind to PHEL whereas PHEL is not immunogenic.Thus, a single amino acid substitution in a synthetic peptide converts a nonresponder mouse strain into a responder one. Anti‐PHEL antibodies demonstrate a higher binding to HEL than anti‐PREL antibodies, indicating that phenylalanine at position 3 is important for induction of anti‐peptide antibodies able to recognize native HEL. At the T cell level the two peptides show very high bidirectional cross‐reactivity between themselves and with HEL for interleukin 2 production, antigen‐specific proliferation and delayed‐type hypersensitivity response, whereas conservation of phenylalanine at position 3 is required for induction of suppressor cells cross‐reactive with HEL. This indicates that the N‐terminal region of HEL contains epitope(s) able to induce the same level of helper T cell activity as the native HEL molecule. However, helper T cells do not discriminate between PHEL and PREL whereas phenylalanine at position 3 is critical for HEL‐specific suppressor T cell induction.
Requirements for growth of immature thymocytes from fetal and adult mice in vitro
Authors: Palacios Ronald , Boehmer Harald Von 
Published: February 2007

AbstractWe report here defined culture conditions that allow reproducibly the growth of the majority of immature thymocytes from both fetal (14–15 days of gestation) and adult mice. The combination of phorbol myristate acetate (PMA), ionomycin and recombinant interleukin 2 (IL2) is both sufficient and necessary to induce growth of about 1/6.2 (range 1/3–1/9) and 1/4.3 (range 1/2–1/7) immature thymocytes from adult and fetal mice, respectively, in serum‐free cultures. Several other combinations tested (e.g. PMA + IL2, concanavalin A + IL2) were poorly or not active. None of the agents tested alone (PMA, ionomycin, concanavalin A, pokeweed mitogen, IL2) had any effect. We found no evidence for a role of IL1 and IL3 on growth of these cells. The growth of activated immature thymocytes from either fetal or adult mice was inhibited by a monoclonal antibody against mouse IL2 receptors.Under the same conditions that stimulated growth of most immature thymocytes, they did not mature into cells expressing Lyt‐2, L3T4 or T cell antigen receptor (KJ16) after 7 to 15 days of continuous proliferation in culture. Nor did they give rise to cells with cytolytic activity after 7–9 days of culture. In some but not all experiments cultures of immature thymocytes from adult mice but not from fetal mice generated cells (1 out of 120–310) with helper function for B lymphocytes.While we confirmed here that ∼50–70% freshly isolated immature thymocytes express receptors for IL2, our results indicate that these cells need to be activated (by e.g. PMA + ionomycin) to respond to IL2. A possible mechanism to account for the expression of nonfunctionally competent IL 2 receptors is proposed and our results concerning the maturation of immature thymocytes in vitro are discussed.
High antigen concentration inhibits T cell proliferation but not interleukin 2 production: Examination of limiting dilution microcultures and T cell clones
Authors: Ceredig Rhodri , Corradin Giampietro 
Published: February 2007

AbstractThe effect of high antigen dose on the activation of cytochrome c peptide‐primed lymph node cells was determined in several strains of mice by a limiting dilution analysis. It was found that proliferation of cytochrome c peptide‐specific T cells was completely inhibited at high antigen concentration in C57BL/6 but only partially in DBA mice and had no effect in SJL mice. Clones derived from DBA mice showed a differential capacity to be inhibited by high antigen dose. On the other hand, interleukin 2 moduction by these clones was not impaired regardless of the antigen concentrations used.
Monocyte‐dependent induction of proliferation of human peripheral T cells by recombinant interleukin 2
Authors: Roosnek Eddy E. , Brouwer Mieke C. , Kipp J. Bart , Aarden Lucien A. 
Published: February 2007

AbstractThe in vitro proliferation of human peripheral lymphocytes induced by interleukin 2 (IL 2), a product of cDNA, cloned in E. coli has been studied. The maximal mitogenic signal is given by concentrations ≦2.5 U/ml. Due to growth factor consumption, at least 10 U/ml are needed to maintain a logarithmic response until day 6. The anti‐Tac antibody, directed against the IL2 receptor, effectively blocks this response, but we could not obtain a decrease of IL2‐reactive cells by depletion of putative in vivo activated Tac+ cells, using this antibody and a fluorescence‐activated cell sorter.Depletion of Leu 7+ and Leu 11b+ cells does not cause a decrease of the response, which indicates that the responding cells are not confined to the natural killer lineage. By simultaneous staining of cell‐surface markers and DNA, the nature of the proliferating cell was determined. More than 90% of the dividing cells expressed HLA class II and the Tac antigen, whereas the lymphocyte populations, defined by the surface markers Leu 2, Leu 3, Leu 4, Leu 7 and Leu 11b, were all represented in the dividing cells. The magnitude of the response was proportional to the number of monocytes present in the culture. Depletion of monocytes completely abrogated the response, whereas an increase in the number of monocytes to a 1:1 ratio with lymphocytes caused a 2‐fold increase in proliferation. However, purified T cells do proliferate to IL 2 when cultured in the presence of a supernatant that was harvested from a 2‐day culture of adherent monocytes. The proliferation‐inducing activity in the supernatant eluted with apparent molecular weights of 15 000 and 75 000 on an Ultrogel AcA‐54 column. Therefore, we conclude that in vitro, in the presence of an IL 1‐like activity produced by monocytes, IL2 is mitogenic for a population of T cells.
Autoimmunity to Thy‐1
Authors: Thomas D. Brian , Giguere Vincent , Graham Christine M. , Oliveira Odete L. P. 
Published: February 2007

AbstractConditions are described for the induction of autoimmunity to Thy‐1 and a large panel of monoclonal CBA and AKR autoantibodies has been characterized. These reveal a hitherto unrecognized complexity at the Thy‐1 locus and evidence for intragenic control. Epitopes recognized by the autoantibodies differed in species and tissue distribution from alloantigenic determinants but their specificity was confirmed by transfection studies with the cloned Thy‐1b gene. The quantitative and qualitative differences in epitope expression between Thy‐1a and Thy‐1b alleles were inherited as single Mendelian traits and in the absence of recombinants, suggesting translational control.
Immune response to diphtheria toxin and to different CNBr fragments: Evidence for different B and T cell reactivities
Authors: Triebel Frédéric , Autran Brigitte , De Roquefeuil Sabine , Falmagne Paul , Debré Patrice 
Published: February 2007

AbstractThe antigenic structure of the diphtheria toxin has been studied in man. B and T cell responses to diphtheria toxoid and to different fragments of the toxin molecule were analyzed in 4 individuals one month after booster immunization. Studies on the B cell response showed that: (a) part of the response was directed against assembled topographic sites; (b) 80% of the response was directed against determinants present on fragment A; (c) the few determinants present on the CNBr peptides of B cross‐react with determinants present on A; and (d) reduction of the second disulfide bridge of fragment B diminishes the response. In contrast to the antibody response, most of the T cell reactivity was directed against the B fragment or CNBr peptides from this fragment. Analysis of the fine specificity of T lymphocyte clones revealed that some CNBr fragments share common T cell determinants. These studies indicate that T and B cell determinants are differently distributed on the molecule and that large cross‐reactivities that are not explained by the analysis of the amino acid sequence could be found at the B and T cell level.
Lymphocyte membrane lipid composition and mitogen responsiveness in chickens: Role of membrane “fluidity”
Authors: Traill Karine N. , Ratheiser Klaus , Pfeilschifter Ruth , Wick Georg 
Published: February 2007

AbstractAfter establishing optimal conditions for measuring the membrane lipid packing density (“fluidity”) of chicken peripheral blood lymphocytes, the fluidity was modulated in vitro by incubation in cholesterol or phospholipid (“active lipid”, AL)‐enriched serum‐free tissue culture medium. The effect of these lipids on mitogen responsiveness was then investigated, the aim being to determine whether the observed enhancement/suppression was membrane mediated, i.e. explainable by fluidity changes.Chicken peripheral blood lymphocytes exhibited no requirement for exogenous cholesterol; low concentrations did not affect the mitogen response while the higher concentrations, which induced a measurable decrease in membrane fluidity, were usually mildly suppressive. Pre‐incubation did not increase this suppressive effect and we believe it not to be membrane mediated.AL, at low concentrations which induced no changes in membrane fluidity, prolonged the phytohemagglutinin response, enhancement being evident only after the peak; we interpret this as a nutrient effect. At the higher concentrations, which induced large increases in fluidity, a transient enhancement was followed by suppression; suppression was delayed in onset when AL was added 4 h after phytohemagglutinin stimulation. It is therefore an early event which may be mediated through changes in membrane fluidity.
T cells bearing unique membrane antigen and their regulatory role in humoral immune response in mice
Authors: Ishida Yasuo , Sekigawa Iwao , Hamaoki Masaru , Takenouchi Toshinao , Yumura Wako , Sato Hidetoshi , Shirai Toshikazu 
Published: February 2007

AbstractThe mutant lpr gene causes a generalized massive T cell proliferation and an associated autoimmune disease in mice. The lpr T cells bear unusual membrane phenotypes and play a causative role in the pathogenesis of autoimmune disease through excess production of some lymphokines. Therefore, the “aberrant” T cells in lpr mice may be normal regulatory T cells in non‐lpr‐bearing mice, if nonproliferative. We thus attempted to produce a xenogeneic monoclonal antibody (ALP‐1) directed against the lpr T cells. The ALP‐1 monoclonal antibody reacted with the antigen Lp‐1 distributing on about one half of the proliferating lymph node cells from MRL/Mp‐lpr/lpr mice but not on the cells from non‐lpr‐bearing mice. Nevertheless, a significant number of Lp‐1+ cells appeared in the lymph node and spleen cells from these normal mice after in vitro stimulation with mitogens. Functional studies revealed that either the treatment with ALP‐1 plus complement of the antigen‐primed splenic T cells from non‐lpr‐bearing mice or the addition of ALP‐1 alone all but completely abolished the development of plaque‐forming cells against sheep red blood cells in T‐B cell co‐culture. Pretreatment of spleen cells with ALP‐1 plus complement, however, did not affect other in vitro T cell functions such as mitogen‐induced proliferative responses, interleukin 2 production, response in mixed lymphocyte culture (MLC) and the MLC‐induced cytotoxic T cell activities. Thus, Lp‐1+ T cells in normal mice are unique T cells that may play an important regulatory role in humoral immune response.
Self‐tolerance to host and donor following HLA‐mismatched bone marrow transplantation
Authors: De Villartay Jean‐Pierre , Griscelli Claude , Fischer Alain 
Published: February 2007

AbstractThe transplantation of T cell‐depleted HLA‐haploidentical bone marrow can correct the severe combined immunodeficiency disease (SCID) caused by the inherited absence of T lymphocytes. Despite a different environment, no severe graft‐vs.‐host reaction occurred and engrafted T lymphocytes became functional. We have studied tolerance of engrafted T lymphocytes to donor and host HLA antigens in four SCID patients who have been transplanted with bone marrow from one of their HLA‐haploidentical parents. Graft‐vs.‐host reaction was prevented by T cell depletion of infused bone marrow using E rosetting and by in vivo administration of cyclosporine A. Subsequent to bone marrow transplantation (BMT), the engrafted T lymphocytes were shown to be unresponsive in vitro towards host cells collected prior to BMT. Generally, this tolerance could not be explained by a suppressive mechanism. Nevertheless, in one patient suppressive cells were found transiently. In contrast to the early appearance of a tolerance towards host, a reactivity of engrafted donor cells towards donor was always observed within the first 300 days post‐grafting. This auto‐reactivity was mediated by T cells of donor origin and its targets were HLA class II molecules (at least HLA‐DR and DQ). The progressive disappearance of this auto‐reactivity was correlated with the engraftment of Ia‐positive cells (monocytes plus B lymphocytes) of donor origin and the achievement of complete immunological reconstitution. In the patient showing the strongest autoreactivity, a donor‐specific T cell line has been grown which was shown to specifically inhibit the proliferative response of donor lymphocytes. Concomittantly, the immunological reconstitution remains poor in this patient. These data suggest that tolerance to HLA class II molecules is dependent on the presence of the relevant HLA class II molecule‐expressing cells allowing the elimination or the suppression of T lymphocytes specifically directed at these molecules.
Limiting dilution analysis of the B cell compartment in human bone marrow
Authors: Hibi Toshifumi , Dosch Hans‐Michael 
Published: February 2007

AbstractMononuclear cells (MNC) obtained from adult rib specimen were investigated for their capacity to produce immunoglobulin (Ig) in vitro. Using limiting dilution analysis 3 populations of B lineage cells could be distinguished. The first produces Ig in culture without any intentional activation. These cells are strictly nonproliferating and sustain extraordinary secretory rates of 5 × 107‐10 × 107 molecules IgG, IgA or IgM/cell/h for at least 2 weaks. They occur at frequencies of 1 × 10‐4‐10 × 10−4 (marrow MNC) or represent 1–5% of marrow B cells. Following exposure to infectious Epstein‐Barr virus (EBV), these cells do not (a) proliferate, (b) express EBV‐determined nuclear antigens (EBNA), (c) enhance their secretory rates or (d) show secretory activity for prolonged time. These cells are therefore EBV resistant. If these cells produced their antibody at similar rates in vivo, then their frequencies would suggest that they could provide up to 2/3 of daily synthetic rates for IgG and IgA and 20–30% of the daily IgM production. The second population of marrow B cells is exclusively committed to IgM production. Following exposure to EBV these cells proliferate, express EBNA and begin to secrete IgM. The third population represents 90% of marrow B cells. In our hands, these cells are unable to produce Ig in vitro.