The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
Naoki Yamamoto - One of the best experts on this subject based on the ideXlab platform.
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catalytic antibody light chain capable of cleaving a Chemokine Receptor CCR 5 peptide with a high reaction rate constant
Biotechnology and Bioengineering, 2004Co-Authors: Yukie Mitsuda, Emi Hifumi, Kumi Tsuruhata, Hiroko Fujinami, Naoki YamamotoAbstract:A monoclonal antibody (MAb), ECL2B-2, was obtained by immunizing a peptide possessing a part of a sequence of a Chemokine Receptor, CCR-5, which is present as a membrane protein on the macrophage surface, and which plays an important role in human immunodeficiency virus (HIV) infection. From the DNA and the deduced amino acid sequences of the light and heavy chains of ECL2B-2 MAb, molecular modeling was conducted to calculate the steric conformation of the antibody. Modeling suggested that the structure of ECL2B-2 could possess one or two catalytic triad(s), composed of Asp1, Ser27a (or Ser27e), and His93 (or His27d), in the light chain of ECL2B-2. The three amino acid residues, Asp1, Ser27a, and His93, are identical to those of catalytic antibody light chains such as VIPase and i41SL1-2. The light chain of ECL2B-2 MAb degraded the antigenic peptide CCR-5 within about 100 h. Surprisingly, the light chain had a very high catalytic reaction rate constant (kcat) of 2.23 min−1, which is greater by factors of tens to hundreds than those of natural catalytic antibodies obtained previously. The heavy chain of ECL2B-2 MAb, which has no catalytic triad because of a lack of His residue, did not degrade the CCR-5 peptide. © 2004 Wiley Periodicals, Inc.
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Catalytic antibody light chain capable of cleaving a Chemokine Receptor CCR‐5 peptide with a high reaction rate constant
Biotechnology and Bioengineering, 2004Co-Authors: Yukie Mitsuda, Emi Hifumi, Kumi Tsuruhata, Hiroko Fujinami, Naoki YamamotoAbstract:A monoclonal antibody (MAb), ECL2B-2, was obtained by immunizing a peptide possessing a part of a sequence of a Chemokine Receptor, CCR-5, which is present as a membrane protein on the macrophage surface, and which plays an important role in human immunodeficiency virus (HIV) infection. From the DNA and the deduced amino acid sequences of the light and heavy chains of ECL2B-2 MAb, molecular modeling was conducted to calculate the steric conformation of the antibody. Modeling suggested that the structure of ECL2B-2 could possess one or two catalytic triad(s), composed of Asp1, Ser27a (or Ser27e), and His93 (or His27d), in the light chain of ECL2B-2. The three amino acid residues, Asp1, Ser27a, and His93, are identical to those of catalytic antibody light chains such as VIPase and i41SL1-2. The light chain of ECL2B-2 MAb degraded the antigenic peptide CCR-5 within about 100 h. Surprisingly, the light chain had a very high catalytic reaction rate constant (kcat) of 2.23 min−1, which is greater by factors of tens to hundreds than those of natural catalytic antibodies obtained previously. The heavy chain of ECL2B-2 MAb, which has no catalytic triad because of a lack of His residue, did not degrade the CCR-5 peptide. © 2004 Wiley Periodicals, Inc.
Joseph A. Hedrick - One of the best experts on this subject based on the ideXlab platform.
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The Kaposi's Sarcoma–related Herpesvirus (KSHV)-encoded Chemokine vMIP-I is a Specific Agonist for the CC Chemokine Receptor (CCR)8
Journal of Experimental Medicine, 1999Co-Authors: Michael J. Endres, Charles G. Garlisi, Hong Xiao, Lixin Shan, Joseph A. HedrickAbstract:The Kaposi's sarcoma–related herpesvirus (KSHV), also designated human herpesvirus 8, is the presumed etiologic agent of Kaposi's sarcoma and certain lymphomas. Although KSHV encodes several Chemokine homologues (viral macrophage inflammatory protein [vMIP]-I, -II, and -III), only vMIP-II has been functionally characterized. We report here that vMIP-I is a specific agonist for the CC Chemokine Receptor (CCR)8 that is preferentially expressed on Th2 T cells. Y3 cells transfected with CCR8 produced a calcium flux in response to vMIP-I and responded vigorously in in vitro chemotaxis assays. In competition binding experiments, the interaction of vMIP-I with CCR8 was shown to be specific and of high affinity. In contrast to its agonist activity at CCR8, vMIP-I did not interact with CCR5 or any of 11 other Receptors examined. Furthermore, vMIP-I was unable to inhibit CCR5-mediated HIV infection. These findings suggest that expression of vMIP-I by KSHV may influence the Th1/Th2 balance of the host immune response.
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the kaposi s sarcoma related herpesvirus kshv encoded Chemokine vmip i is a specific agonist for the cc Chemokine Receptor CCR 8
Journal of Experimental Medicine, 1999Co-Authors: Michael J. Endres, Charles G. Garlisi, Hong Xiao, Lixin Shan, Joseph A. HedrickAbstract:The Kaposi's sarcoma–related herpesvirus (KSHV), also designated human herpesvirus 8, is the presumed etiologic agent of Kaposi's sarcoma and certain lymphomas. Although KSHV encodes several Chemokine homologues (viral macrophage inflammatory protein [vMIP]-I, -II, and -III), only vMIP-II has been functionally characterized. We report here that vMIP-I is a specific agonist for the CC Chemokine Receptor (CCR)8 that is preferentially expressed on Th2 T cells. Y3 cells transfected with CCR8 produced a calcium flux in response to vMIP-I and responded vigorously in in vitro chemotaxis assays. In competition binding experiments, the interaction of vMIP-I with CCR8 was shown to be specific and of high affinity. In contrast to its agonist activity at CCR8, vMIP-I did not interact with CCR5 or any of 11 other Receptors examined. Furthermore, vMIP-I was unable to inhibit CCR5-mediated HIV infection. These findings suggest that expression of vMIP-I by KSHV may influence the Th1/Th2 balance of the host immune response.
Seema S Ahuja - One of the best experts on this subject based on the ideXlab platform.
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cd8α dendritic cells improve collagen induced arthritis in cc Chemokine Receptor CCR 2 deficient mice
Immunobiology, 2011Co-Authors: Jessica M Ibarra, Marlon P Quinones, Fabio Jimenez, Hernan Martinez, Carlos A Estrada, Seema S AhujaAbstract:Objective Dendritic cells (DCs) have long been recognized as potential therapeutic targets of rheumatoid arthritis (RA). Increasing evidence has showed that DCs are capable of suppressing autoimmunity by expanding FoxP3+ regulatory T cells (Treg), which in turn exert immunosuppression by increasing TGFβ-1. In the SKG mice, activated DC prime autoreactive T cells causing autoantibody production and an inflammatory arthritic response. Recently, we reported that CC-Chemokine Receptor-2 deficient (CCR2−/−) mice had impaired DCs migration and reduced CD8α+ DCs in the C57Bl/6J mice strain and that these mice were more susceptible to collagen antibody-induced arthritis (CAIA), compared to wild type mice. To examine the mechanism by which DCs contribute to the increased susceptibility of arthritis in CCR2−/− mice, we tested the hypothesis that CD8α+ DCs are protective (tolerogenic) against autoimmune arthritis by examining the role of CD8α+ DCs in CCR2−/− and SKG mice.
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cc Chemokine Receptor CCR 2 is required for langerhans cell migration and localization of t helper cell type 1 th1 inducing dendritic cells absence of CCR2 shifts the leishmania major resistant phenotype to a susceptible state dominated by th2 cytoki
Journal of Experimental Medicine, 2000Co-Authors: Naoko Sato, Sunil K Ahuja, Marlon P Quinones, Vannessa Kostecki, Robert L Reddick, Peter C Melby, William A Kuziel, Seema S AhujaAbstract:There is growing evidence that Chemokines and their Receptors regulate the movement and interaction of antigen-presenting cells such as dendritic cells (DCs) and T cells. We tested the hypothesis that the CC Chemokine Receptor (CCR)2 and CCR5 and the Chemokine macrophage inflammatory protein (MIP)-1α, a ligand for CCR5, influence DC migration and localization. We found that deficiency of CCR2 but not CCR5 or MIP-1α led to distinct defects in DC biology. Langerhans cell (skin DC) density in CCR2-null mice was normal, and their ability to migrate into the dermis was intact; however, their migration to the draining lymph nodes was markedly impaired. CCR2-null mice had lower numbers of DCs in the spleen, and this was primarily due to a reduction in the CD8α1 T helper cell type 1 (Th1)-inducing subset of DCs. Additionally, there was a block in the Leishmania major infection–induced relocalization of splenic DCs from the marginal zone to the T cell areas. We propose that these DC defects, in conjunction with increased expression of B lymphocyte chemoattractant, a B cell–specific Chemokine, may collectively contribute to the striking B cell outgrowth and Th2 cytokine–biased nonhealing phenotype that we observed in CCR2-deficient mice infected with L. major. This disease phenotype in mice with an L. major–resistant genetic background but lacking CCR2 is strikingly reminiscent of that observed typically in mice with an L. major–susceptible genetic background. Thus, CCR2 is an important determinant of not only DC migration and localization but also the development of protective cell-mediated immune responses to L. major.
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defects in the generation of ifn γ are overcome to control infection with leishmania donovani in cc Chemokine Receptor CCR 5 macrophage inflammatory protein 1α or CCR2 deficient mice
Journal of Immunology, 1999Co-Authors: Naoko Sato, Sunil K Ahuja, Vannessa Kostecki, Robert L Reddick, Peter C Melby, William A Kuziel, Weiguo Zhao, Nobuyo Maeda, Seema S AhujaAbstract:We investigated the immune responses in mice lacking CCR2, CCR5, or macrophage inflammatory protein-1α (MIP-1α), a ligand for CCR5, in two situations: following T cell stimulation or after challenge with Leishmania donovani , an intracellular microbe whose control is dependent on a Th1 immune response. Mice deficient in CCR5, MIP-1α, or CCR2 had reduced IFN-γ responses following ligation of the TCR. Reduced IFN-γ responses following PMA and ionomycin were also observed in CD8 + T cells of CCR5 −/− and CCR2 −/− mice. During the early phases of infection, all three knockout mice had low Ag-specific IFN-γ responses. However, this reduced IFN-γ response was overcome during a state of persistent Ag stimulation (chronic infection), and was not associated with an adverse parasitologic outcome in any of the gene-targeted mouse strains. To the contrary, during the late phase of infection, an exaggerated Ag-specific IFN-γ response was evident in CCR5 −/− and MIP-1α −/− mice, and this correlated with an enhanced control of parasite replication. Although granuloma formation was abnormal in each of the knockout mice, there was no correlation between the number or architecture of the granulomas and parasite burden. Collectively, these findings indicate an important role for CCR5, MIP-1α, and CCR2 in granulomatous inflammation, and that CCR5 and MIP-1α, possibly acting through CCR5, might play a deleterious role in the outcome of chronic L. donovani infection. Our data also suggest that there might be cross-talk between TCR and Chemokine Receptor signaling pathways.
Yukie Mitsuda - One of the best experts on this subject based on the ideXlab platform.
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catalytic antibody light chain capable of cleaving a Chemokine Receptor CCR 5 peptide with a high reaction rate constant
Biotechnology and Bioengineering, 2004Co-Authors: Yukie Mitsuda, Emi Hifumi, Kumi Tsuruhata, Hiroko Fujinami, Naoki YamamotoAbstract:A monoclonal antibody (MAb), ECL2B-2, was obtained by immunizing a peptide possessing a part of a sequence of a Chemokine Receptor, CCR-5, which is present as a membrane protein on the macrophage surface, and which plays an important role in human immunodeficiency virus (HIV) infection. From the DNA and the deduced amino acid sequences of the light and heavy chains of ECL2B-2 MAb, molecular modeling was conducted to calculate the steric conformation of the antibody. Modeling suggested that the structure of ECL2B-2 could possess one or two catalytic triad(s), composed of Asp1, Ser27a (or Ser27e), and His93 (or His27d), in the light chain of ECL2B-2. The three amino acid residues, Asp1, Ser27a, and His93, are identical to those of catalytic antibody light chains such as VIPase and i41SL1-2. The light chain of ECL2B-2 MAb degraded the antigenic peptide CCR-5 within about 100 h. Surprisingly, the light chain had a very high catalytic reaction rate constant (kcat) of 2.23 min−1, which is greater by factors of tens to hundreds than those of natural catalytic antibodies obtained previously. The heavy chain of ECL2B-2 MAb, which has no catalytic triad because of a lack of His residue, did not degrade the CCR-5 peptide. © 2004 Wiley Periodicals, Inc.
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Catalytic antibody light chain capable of cleaving a Chemokine Receptor CCR‐5 peptide with a high reaction rate constant
Biotechnology and Bioengineering, 2004Co-Authors: Yukie Mitsuda, Emi Hifumi, Kumi Tsuruhata, Hiroko Fujinami, Naoki YamamotoAbstract:A monoclonal antibody (MAb), ECL2B-2, was obtained by immunizing a peptide possessing a part of a sequence of a Chemokine Receptor, CCR-5, which is present as a membrane protein on the macrophage surface, and which plays an important role in human immunodeficiency virus (HIV) infection. From the DNA and the deduced amino acid sequences of the light and heavy chains of ECL2B-2 MAb, molecular modeling was conducted to calculate the steric conformation of the antibody. Modeling suggested that the structure of ECL2B-2 could possess one or two catalytic triad(s), composed of Asp1, Ser27a (or Ser27e), and His93 (or His27d), in the light chain of ECL2B-2. The three amino acid residues, Asp1, Ser27a, and His93, are identical to those of catalytic antibody light chains such as VIPase and i41SL1-2. The light chain of ECL2B-2 MAb degraded the antigenic peptide CCR-5 within about 100 h. Surprisingly, the light chain had a very high catalytic reaction rate constant (kcat) of 2.23 min−1, which is greater by factors of tens to hundreds than those of natural catalytic antibodies obtained previously. The heavy chain of ECL2B-2 MAb, which has no catalytic triad because of a lack of His residue, did not degrade the CCR-5 peptide. © 2004 Wiley Periodicals, Inc.
Michael J. Endres - One of the best experts on this subject based on the ideXlab platform.
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The Kaposi's Sarcoma–related Herpesvirus (KSHV)-encoded Chemokine vMIP-I is a Specific Agonist for the CC Chemokine Receptor (CCR)8
Journal of Experimental Medicine, 1999Co-Authors: Michael J. Endres, Charles G. Garlisi, Hong Xiao, Lixin Shan, Joseph A. HedrickAbstract:The Kaposi's sarcoma–related herpesvirus (KSHV), also designated human herpesvirus 8, is the presumed etiologic agent of Kaposi's sarcoma and certain lymphomas. Although KSHV encodes several Chemokine homologues (viral macrophage inflammatory protein [vMIP]-I, -II, and -III), only vMIP-II has been functionally characterized. We report here that vMIP-I is a specific agonist for the CC Chemokine Receptor (CCR)8 that is preferentially expressed on Th2 T cells. Y3 cells transfected with CCR8 produced a calcium flux in response to vMIP-I and responded vigorously in in vitro chemotaxis assays. In competition binding experiments, the interaction of vMIP-I with CCR8 was shown to be specific and of high affinity. In contrast to its agonist activity at CCR8, vMIP-I did not interact with CCR5 or any of 11 other Receptors examined. Furthermore, vMIP-I was unable to inhibit CCR5-mediated HIV infection. These findings suggest that expression of vMIP-I by KSHV may influence the Th1/Th2 balance of the host immune response.
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the kaposi s sarcoma related herpesvirus kshv encoded Chemokine vmip i is a specific agonist for the cc Chemokine Receptor CCR 8
Journal of Experimental Medicine, 1999Co-Authors: Michael J. Endres, Charles G. Garlisi, Hong Xiao, Lixin Shan, Joseph A. HedrickAbstract:The Kaposi's sarcoma–related herpesvirus (KSHV), also designated human herpesvirus 8, is the presumed etiologic agent of Kaposi's sarcoma and certain lymphomas. Although KSHV encodes several Chemokine homologues (viral macrophage inflammatory protein [vMIP]-I, -II, and -III), only vMIP-II has been functionally characterized. We report here that vMIP-I is a specific agonist for the CC Chemokine Receptor (CCR)8 that is preferentially expressed on Th2 T cells. Y3 cells transfected with CCR8 produced a calcium flux in response to vMIP-I and responded vigorously in in vitro chemotaxis assays. In competition binding experiments, the interaction of vMIP-I with CCR8 was shown to be specific and of high affinity. In contrast to its agonist activity at CCR8, vMIP-I did not interact with CCR5 or any of 11 other Receptors examined. Furthermore, vMIP-I was unable to inhibit CCR5-mediated HIV infection. These findings suggest that expression of vMIP-I by KSHV may influence the Th1/Th2 balance of the host immune response.