bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lateral organization of the ICAM‐1 molecule at the surface of human lymphoblasts: A possible model for its co‐distribution with the IL‐2 receptor, class I and class II HLA molecules
Authors: Bene László , Balázs Margit , Matkó János , Möst Johannes , Dierich Manfred P. , Szöllsi János , Damjanovich Sándor 
Published: March 2007

AbstractLateral distribution of the ICAM‐1 molecule and its topological relationship (mutual proximity) to the heavy and light chains of class I HLA molecules, HLA‐DR and interleukin‐2 receptor α‐chain (IL‐2Rα) were studied in the plasma membrane of HUT‐102B2 T and JY B lymphoblastoid cell lines by the technique of flow cytometric energy transfer (FCET). Effects of adherency and treatments with recombinant interferon‐γ or tumor necrosis factor‐α on the relative expression level of ICAM‐1 to the above cell surface proteins were also investigated. While the cytokines did not significantly affect the ICAM‐1 level of either cell line, an increased ICAM‐1 expression was found on adherent JY cells. The ICAM‐1 expression varied significantly with the cell cycle and culture conditions, as well. The statistical analysis of the differences observed in the energy transfer efficiency histograms resulted in a possible model of lateral co‐distribution of these proteins in the plasma membrane. These two‐dimensional patterns proved to be different for T and B lymphoma lines. ICAM‐1 molecules showed a high degree of self‐ssociation on HUT‐102B2 (T) cells, while they were mainly expressed as monomers on the surface of JY (B) cells. Both cells showed a significant (ca. 30 %) difference between densities of the heavy and light chains of class I HLA antigen, suggesting a substantial amount of β2‐microglobulin free heavy chains on these cell lines. The class I HLA molecules also showed partial self‐association, but on both cell lines. The β2‐microglobulin and the heavy chain of the class I HLA showed strongly different proximities to the IL‐2Rα, HLA‐DR and ICAM‐1 molecules, indicating that their orientations relative to the other proteins are dissimilar. IL‐2Rα molecules of the HUT‐102B2 (T) cells are located mostly in the vicinity of the β2‐microglobulin. In contrast, the local density of HLA‐DR antigens is higher in the proximity of the heavy chain than in the vicinity of the β2‐microglobulin. The possible functional significance of these protein patterns is also discussed herein.
Autologous cytolytic T lymphocytes recognize a MAGE‐1 nonapeptide on melanomas expressing HLA‐Cw* 1601
Authors: Bruggen Pierre Van Der , Szikora Jean‐Pierre , Boël Pascale , Wildmann Claude , Somville Michel , Sensi Marialuisa , Boon Thierry 
Published: March 2007

AbstractHuman melanoma cell line MZ2‐MEL expresses several antigens recognized by autologous cytolytic T lymphocyte (CTL) clones. We reported previously the identification of a gene, named MAGE‐1, which codes for antigen MZ2‐E which is presented by HLA‐A1. Gene MAGE‐1 is expressed in many tumors of several types but not in normal tissues except for testis. We show here that gene MAGE‐1 directs the expression of another antigen recognized by CTL on the MZ2‐MEL cells. This antigen, which was named MZ2‐Bb, consists of MAGE‐1‐encoded peptide SAYGEPRKL bound to major histocompatibility molecule HLA‐Cw* 1601. The HLA‐Cw* 1601 allele was found to be expressed by 7 out of 99 individuals from a Caucasian population. Our results extend the range of tumor patients who could be eligible for immunization against MAGE antigens.
Presentation of a horse cytochrome c peptide by multiple H‐2b class I major histocompatibility complex (MHC) molecules to C57BL/6‐ and bm1‐derived cytotoxic T lymphocytes: Presence of a single MHC anchor residue may confer efficient peptide‐specific CTL recognition
Authors: Sheil James M. , Schell Todd D. , Shepherd Sara E. , Klimo Gerald F. , Kioschos John M. , Paterson Yvonne 
Published: March 2007

AbstractIn this study the immunogenic tryptic fragment from a horse cytochrome c (cyt c) digest recognized by cytotoxic T lymphocytes (CTL), induced by in vitro peptide stimulation from C57BL/6 (B6) and mutant B6.C‐H‐2bm1 (bm1) mice is identified. An identical sequence, p40—53, is recognized by CTL from both B6 and bm1 mice. In addition, both B6 and bm1 cloned CTL lines display unusual major histocompatibility complex (MHC) class I‐restricted recognition of this peptide in that they respond to it in the context of H‐2Kb, H‐2Db, and H‐2Kbm1 class I molecules, although the sequence lacks the usual structural Kb and Db peptide‐binding motifs. Truncated analogues which resemble the lengths of naturally processed MHC class I‐presented peptides, confer reactivity for B6 and bm1 CTL against EL4 (H‐2b) targets as well as the L cell transfectants, L + Kb, L + Db, and L + Kbm1. The antigenic peptide with the greatest potency is p41—49, which appears to be generated by angiotensin converting enzyme cleavage of the full‐length p40—53 tryptic peptide. The minimum antigenic peptide recognized by both B6 and bm1 CTL, and which targets lysis on each of the transfectants, is the hexamer p43—48 peptide from horse cyt c. Residues Pro44 and Thr47, which occupy polymorphic positions with respect to other species‐variant cyt c molecules, influence recognition of these peptides differently for the B6 and bm1 CTL. The ability of H‐2Kb, H‐2Db, and mutant H‐2Kbm1 class I molecules to present the same peptide to a single cloned CTL is discussed in the context of current knowledge of peptide anchor residues and side chain‐specific binding pockets in the MHC class I peptide‐binding site.
Differential effects of cyclic adenosine 3′, 5′‐monophosphate on T cell cytotoxicity
Authors: Østenstad Bjørn , Harboe Morten , Lea Tor 
Published: March 2007

AbstractWe have investigated natural killer cell and T cell cytotoxicity using different assays and report a dual effect of cyclic adenosine 3′, 5′‐monophosphate (cAMP) on T cell cytotoxicity depending on the activation status of the effector cell and the test system in question. cAMP enhanced the capacity of pre‐activated T cells to induce DNA fragmentation in the target cell, while it inhibited spontaneous T cell cytotoxicity and natural killer cell cytotoxicity in conventional assays based on 51Cr release. The enhancement was most likely mediated by the cAMP‐dependent protein kinase type II (cAKII), which is the particular isoform in T cells associated with the centrosome and the microtubule organizing center (MTOC). We show the complete co‐localization of the cAKII with the centrosome after conjugate formation. Furthermore, the reorganization of the MTOC following conjugate formation brings the type II kinase into close proximity with the T lymphocyte membrane area engaged in the effector‐target interaction. Functional studies utilizing different cAMP‐analog combinations further substantiate the involvement of the type II kinase.
Distinct binding of T lymphocytes to ICAM‐1, ‐2 or ‐3 upon activation of LFA‐1
Authors: Binnerts Minke E. , van Kooyk Yvette , Simmons David L. , Figdor Carl G. 
Published: March 2007

AbstractLFA‐1 (CD11a/CD18) mediates leukocyte adhesion by binding to one of its ligands: ICAM‐1, ICAM‐2 or ICAM‐3. Here, we investigated whether stimuli known to induce adhesion to ICAM‐1 were also capable of inducing LFA‐1‐mediated adhesion of T lymphocytes to ICAM‐2 and ‐3 transfectants. We observed that phorbol 12‐myristate 13‐acetate, Mn2+, cross‐linking of CD3 or activating antibodies against LFA‐1 enhanced LFA‐1‐mediated T cell adhesion to ICAM‐2 and ‐3, although to a lesser extent than to ICAM‐1. These results indicate that, similar to what has been reported for adhesion to ICAM‐1, activation of LFA‐1 is also required for adhesion to ICAM‐2 and ‐3. Furthermore, the results suggest that ICAM‐1 is the major ligand for LFA‐1 on activated T lymphocytes. Interestingly, we observed that in contrast to activating antibodies against CD18, activating antibodies against CD11a were incapable of inducing adhesion of LFA‐1 to all three ligands. The antibody MEM‐83 stimulated binding to ICAM‐1, while at the same time inhibiting the interaction of LFA‐1 with ICAM‐2 and ‐3. The antibody NKI‐L16 selectively induced adhesion to ICAM‐1 and ‐2, but not to ICAM‐3. Our results suggest that different conformations of LFA‐1 are required to support adhesion to ICAM‐1, ‐2 or ‐3, and that ligands may bind on different sites of the LFA‐1 molecule.
Inhibition of human IgE synthesis by anti‐IgE antibodies requires divalent recognition
Authors: Stämpfli Martin R. , Miescher Sylvia , Aebischer Iwan , Zürcher Adrian W. , Stadler Beda M. 
Published: March 2007

AbstractWe used a selection of well‐characterized murine monoclonal anti‐IgE antibodies to investigate their effect on human in vitro IgE synthesis. We found anti‐IgE antibodies that either inhibited or enhanced interleukin‐4 plus anti‐CD40‐induced in vitro IgE synthesis in peripheral blood mononuclear cells (PBMC). This differential activity was isotype specific as neither IgM nor IgG synthesis were affected. Interestingly, only coding IgE mRNA was down‐regulated, whereas germ‐line ε RNA expression was not influenced by anti‐IgE monoclonal antibody (mAb). On purified B cells all anti‐IgE mAb inhibited interleukin‐4 plus anti‐CD40‐induced IgE synthesis, implying a role of non‐B cells for the enhancing activity observed in PBMC. Using Fab and F(ab')2 of an inhibitory anti‐IgE mAb we could show that divalent recognition was required for inhibition of IgE synthesis.
Cathepsin D, but not cathepsin B, releases T cell stimulatory fragments from lysozyme that are functional in the context of multiple murine class II MHC molecules
Authors: Van Noort Johannes M. , Jacobs Marike J. M. 
Published: March 2007

AbstractIn this study, the major endosomal/lysosomal proteases cathepsin D and cathepsin B were tested on their ability to release T cell stimulatory peptides from hen egg white lysozyme (HEL) in vitro. Whereas neither enzyme could cleave unreduced HEL under mild conditions, reduced HEL was readily cleaved by cathepsin D but not by cathepsin B. Instead, cathepsin B was found to be very active in the trimming of HEL peptides after their release by cathepsin D.Following high‐performance liquid chromatography (HPLC) fractionation, cathepsin D‐released HEL fragments were screened for recognition by HEL‐specific T cells from three strains of mice, i.e. B10. A (H‐2a), C57BL/6 (H‐2b) and BALB/c (H‐2d). Peptides in a large number of different HPLC fractions triggered significant T cell responses in all three strains. Interestingly, the response profiles of T cells from the three different strains showed marked similarities. Also, several individual synthetic HEL sequences corresponding to selected cathepsin D‐released fragments were recognized by murine T cells in the context of all three major histocompatibility complex (MHC) haplotypes tested.Our data suggest that cathepsin D rather than cathepsin B may play a central role in the initial release of HEL fragments during endosomal/lysosomal processing. The relatively long HEL fragments released by cathepsin D, containing about 20—30 amino acid residues, are significantly more promiscuous in murine class II MHC binding than the shorter synthetic HEL sequences previously employed by others for the delineation of HEL epitopes. Extensive documentation of HEL epitopes in previous investigations indicate that this promiscuity cannot be explained by simply assuming that longer peptides contain additional epitopes. Rather, an increased peptide length by itself appears to promote promiscuous MHC binding.
Detergent‐enhanced dissociation of endogenous peptides from PI‐DRB1*0401
Authors: Buelow Roland , Kuo Stephanie , Paborsky Lisa , Wilson K. Jeff , Rothbard Jonathan B. 
Published: March 2007

AbstractA variety of detergents have been shown to catalyze the dissociation of bound peptides from a soluble from of DRB1*0401. By using a class II molecule lacking the hydrophobic transmembrane region, the need for solubilizing the transmembrane protein was removed and enabled the specific interaction between the class II protein and the amphiphile to be identified. The presence of detergent increased the rate of association of added peptide and the percent occupancy of the receptor, presumably because the dissociation of endogenous peptide was the rate‐limiting step in binding. The data help explain the differences reported between peptide binding to class II proteins on the surface of cells and binding to class II proteins solubilized in detergent. The interaction did not correlate with the critical micellar concentration of the detergent nor were all amphiphilic structures equally effective, consistent with a specific interaction between the amphiphile and the MHC class II protein. Of the eight detergents examined, octyl glucoside was the most efficient. These experiments did not distinguish between an allosteric mechanism or direct competition with the peptide for binding.
Intercellular adhesion molecules (ICAM)‐1 ICAM‐2 and ICAM‐3 function as counter‐receptors for lymphocyte function‐associated molecule 1 in human immunodeficiency virus‐mediated syncytia formation
Authors: Butini Luca , De Fougerolles Antonin R. , Vaccarezza Mauro , Graziosi Cecilia , Cohen David I. , Montroni Maria , Springer Timothy A. , Pantaleo Giuseppe , Fauci Anthony S. 
Published: March 2007

AbstractIt has been previously demonstrated that lymphocyte function‐associated molecule 1 (LFA‐1) plays a major role in human immunodeficiency virus (HIV)‐mediated syncytia formation. In the present study we investigated the involvement of intercellular adhesion molecule‐1 (ICAM‐1), ICAM‐2 and ICAM‐3 in the process. The ability of monoclonal antibodies (mAb) directed against ICAM‐1, ICAM‐2 and ICAM‐3 to block syncytia was analyzed either in phytohemagglutinin (PHA)‐activated lymphocytes infected in vitro with primary or laboratory strains of HIV or by coculturing a T cell line stably expressing HIV envelope with PHA‐activated lymphocytes. Complete inhibition of syncytia formation was observed only by the simultaneous addition to the cell cultures of all (i.e. anti‐ICAM‐1, anti‐ICAM‐2 and anti‐ICAM‐3) mAb. These results indicate that the interaction between LFA‐1 and ICAM is a critical step in HIV‐mediated syncytia formation, and that ICAM‐1, ICAM‐2 and ICAM‐3 are the receptor molecules for the LFA‐1‐dependent syncytia formation.
Class II major histocompatibility complex‐restricted T cell function in CD4‐deficient mice
Authors: Rahemtulla Amin , Kündig Thomas M. , Narendran Arumugabadiv , Bachmann Martin F. , Julius Michael , Paige Christopher J. , Ohashi Pamela S. , Zinkernagel Rolf M. , Mak Tak W. 
Published: March 2007

AbstractPreviously, we and others have demonstrated that CD4‐deficient mice have a normal number of T cells and B cells with a significant population of CD4‐8‐TcRαβ+ T cells. Surprisingly, however, these mice lacking CD4 show in vivo immunoglobulin isotype class switching from IgM to IgG in response to sheep erythrocytes and vesicular stomatitis virus. In this study we have depleted various subpopulations of T cells in vivo and shown that the population of CD4‐8‐TcRαβ+ T cells is responsible for providing “help” in the antibody response of CD4‐deficient mice to vesicular stomatitis virus infection. We have used antigen‐specific proliferation assays and blocking studies with class I and II major histocompatibility complex (MHC)‐specific purified antibodies to show that these cells are class II MHC‐restricted in responses against the T cell‐dependent antigen keyhole limpet hemocyanin (KLH). Finally, phenotypic analysis of the CD4‐ CD8‐thymocytes in CD4‐deficient mice shows that these cells have a more mature phenotype than the CD4‐8‐ thymocytes in wild type mice. These results indicate that CD4 is not absolutely necessary for positive selection or effector function of class II MHC‐restricted helper T cells.
Experimental allergic encephalomyelitis (EAE) in mice lacking CD4+ T cells
Authors: Koh Dow‐Rhoon , Ho Alexandra , Rahemtulla Amin , Penninger Josef , Mak Tak‐Wah 
Published: March 2007

AbstractLike most experimental autoimmune disease experimental allergic encephalomyelitis (EAE) has been shown to be mediated by CD4+ helper T cells. In vivo antibody blocking studies with anti‐CD4 and adoptive transfer of activated CD4+ T cells indicate the importance of CD4+ cells in disease induction. Fourth backcross generation mutant CD4—/— PL/J mice were immunized with myelin basic protein. Despite the lack CD4+ T cells some of these mice developed EAE, albeit, at a considerably reduced frequency and with variable severity. Furthermore, antigen‐specific T cell proliferation can be demonstrated, indicating some residual helper activity that is major histocompatibility complex class II restricted. This demonstrates that, although the CD4+ T cell is the prime effector cell in EAE, in mice developmentally lacking in CD4, the expanded double‐negative T cells may subserve helper and effector functions.
Development of motility of Langerhans cell through extracellular matrix by in vitro hapten contact
Authors: Kobayashi Yasunobu , Staquet Marie‐Jeanne , Dezutter‐Dambuyant Colette , Schmitt Daniel 
Published: March 2007

AbstractTo study the migration capacity of Langerhans cells in vitro, a reconstituted basement membrane invasion assay (Matrigel assay) was performed. Partially enriched human epidermal Langerhans cell suspensions (6—20%) were incubated with or without haptens [2, 4, 6‐/trinitrobenzenesulfonic acid (TNBS) and fluorescein isothiocyanate (FITC)] or an irritant sodium lauryl sulfate (SLS) in Hanks' balanced salt solution for 10 min at 37°C, and were then used for the invasion assay. Fibroblast‐conditioned medium prepared from human dermal fibroblasts was used as a source of chemoattractants. Non‐treated cells showed a gradual increase in migration of HLA‐DR‐positive cells through the Matrigel‐coated filters in a time‐dependent manner. In vitro TNBS and FITC treatment resulted in a significant stimulation of this migration. By contrast, SLS treatment did not increase the number of migrating cells. The migration capacity of hapten‐treated cells decreased both in the absence of human fibroblast‐conditioned medium and in the presence of this medium in the upper compartment of the chamber, indicating that this medium actually functioned as chemoattractant. Our findings suggest that the contact between hapten and Langerhans cells could be one of the triggers to initiate and/or stimulate Langerhans cell migration from the epidermis to the dermis. In addition, some factors derived from the dermal fibroblasts may promote and regulate the directional migration of Langerhans cells.
Expression of a wide T cell receptor Vβ repertoire in human T lymphocytes derived in vitro from embryonic liver cell precursors
Authors: Poggi Alessandro , Demarest James F. , Costa Paola , Biassoni Roberto , Pella Nicoletta , Pantaleo Giuseppe , Mingari M. Cristina , Moretta Lorenzo 
Published: March 2007

AbstractAs shown recently, CD3+/TcR+ functional T lymphocytes can be derived in culture from embryonic liver cell precursors at a gestational age (6—8 weeks) preceeding the colonization of the epithelial thymus. In this report, we analyzed the Vβ repertoire of T lymphocytes derived from embryonic liver by applying a quantitative reverse transcriptase‐polymerase chain reaction technique. To this end, oligonucleotide primers for Cα or the various human Vβ have been used to study both freshly derived embryonic liver cell suspensions and CD3+/TcR+ populations derived after approximately 6 weeks upon stimulation with 1% phytohemagglutinin and culture in 100 units/ml recombinant interleukin‐2. In order to exclude possible contaminations with mother‐derived T lymphocytes, only T cells displaying both X and Y chromosomal sequences (i.e. derived from male embryos) were further analyzed. While neither Cα nor the various Vβ could be detected in fresh liver cells, Cα and the large majority of Vβ were detected in in vitro cultured populations. The levels of the various Vβ expressed by embryo‐derived T cells was similar to that detected in adult peripheral blood‐derived T lymphocytes. These experiments indicate that the immature liver precursors can potentially give rise in vitro to T cells which express a wide Vβ repertoire and may provide a suitable in vitro system for the analysis of the selection processes mediated by either major histocompatibility complex antigen or superantigens.
Interleukin‐12 regulates the proliferation of Th1, but not Th2 or Th0, clones
Authors: Kennedy Mary K. , Picha Kathleen S. , Shanebeck Kurt D. , Anderson Dirk M. , Grabstein Kenneth H. 
Published: March 2007

AbstractOur results indicate that interleukin (IL)‐12 is an important costimulator of antigen‐dependent proliferation of murine Th1 clones. In addition, we demonstrate that IL‐10 inhibits splenic antigen‐presenting cell (APC)‐dependent proliferation of Th1 clones, at least in part, via down‐regulation of APC‐derived IL‐12. Moreover, the failure of activated B cells to provide costimulation via IL‐12 accounts for their inability to support optimal proliferative responses of Th1 clones. We also show that IL‐12 regulates the ability of Th1 clones to respond to IL‐4 and enhances their proliferation in response to IL‐2, IL‐7, or IL‐15. In contrast, Th2 and Th0 clones appear refractory to the effects of IL‐12 on antigen‐dependent or growth factor‐induced proliferation.
Distinct mouse bone marrow macrophage precursors identified by differential expression of ER‐MP12 and ER‐MP20 antigens
Authors: de Bruijn Marella F. T. R. , Slieker Walentina A. T. , van der Loo Johannes C. M. , Voerman Jane S. A. , van Ewijk Willem , Leenen Pieter J. M. 
Published: March 2007

AbstractThe characterization of early branch points in the differentiation of leukocytes requires identification of precursor cells in the bone marrow. Recently, we produced two monoclonal antibodies, ER‐MP12 and ER‐MP20, which in two‐color flow‐cytometric analysis divide the murine bone marrow into six defined subsets. Here we show, using fluorescence‐activated cell sorting followed by macrophage colony‐stimulating factor‐stimulated culture in soft agar, that precursors of the mononuclear phagocyte system reside only within the ER‐MP12hi20−, ER‐MP12+20+ and ER‐MP12−20hi bone marrow subsets. Together, these subsets comprise 15% of nucleated bone marrow cells. Furthermore, we provide evidence that the macrophage precursors present in these subsets represent successive stages in a maturation sequence where the most immature ER‐MP12hi20− cells develop via the ER‐MP12+20+ stage into ER‐MP12−20hi monocytes.