Abstract：
:Mouse monoclonal antibody AUK12-20 binds to human IL-6 receptor and inhibits IL-6 functions. It has been humanized by CDR-grafting for therapeutic use. In the design of reshaped human AUK12-20 VL region, the human framework regions (FRs) from the human Bence-Jones protein REI were used. The reshaped human AUK12-20 light chain, in combination with chimeric AUK12-20 heavy chain, bound to antigen as well as chimeric AUK12-20 antibody. In the design of reshaped human AUK12-20 VH region, two sets of the human FRs were chosen and compared. One set was from the consensus amino acid sequence for human VH regions subgroup (HSG)-I and the other set was from human antibody HAX, the most similar human VH region found in a database of human immunoglobulin sequences. The HSG-I-based and the HAX-based reshaped human AUK12-20 heavy chains in combination with the reshaped human AUK12-20 light chain, showed approximately 90 and 100% antigen-binding and competition-binding activities as compared to the chimeric or mouse AUK12-20 heavy chains. Most importantly, these humanized antibodies inhibited the IL-6-dependent tumor cell growth as well as the original mouse antibody suggesting that these humanized antibodies could be efficacious in human patients. Our results show that both approaches for the design of reshaped human antibodies can be used for successful humanization. The approach based on FRs from the most similar individual human antibody, however, seemed to be best for designing a reshaped human antibody that mimicked as closely as possible the original mouse antibody.
journal_name
Mol Immunoljournal_title
Molecular immunologyauthors
Sato K,Tsuchiya M,Saldanha J,Koishihara Y,Ohsugi Y,Kishimoto T,Bendig MMdoi
10.1016/0161-5890(94)90115-5subject
Has Abstractpub_date
1994-04-01 00:00:00pages
371-81issue
5eissn
0161-5890issn
1872-9142journal_volume
31pub_type
杂志文章abstract：:The NLRP3 inflammasome constitutes a major antiviral host defense mechanism during influenza virus infection. Inflammasome assembly in virus-infected cells facilitates autocatalytic processing of pro-caspase-1 and subsequent cleavage and secretion of proinflammatory cytokines IL-1β and IL-18. The NLRP3 inflammasome is...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2017.01.023
更新日期：2017-06-01 00:00:00
abstract：:Intercellular adhesion molecule-1 (ICAM-1) functions in leukocyte trafficking, activation, and the formation of the immunological synapse. ICAM-1 is a member of the immunoglobulin superfamily of adhesion proteins, which share a similar structure of repeating Ig-like domains. Many genes in this family, including ICAM-1...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2010.03.005
更新日期：2010-05-01 00:00:00
abstract：OBJECTIVE:Nuclear components targeted by autoantibodies are a characteristic feature of the autoimmune disease systemic lupus erythematosus (SLE). The nucleosome, a major autoantigen, is released in patients with SLE as a result of a disturbed apoptosis and/or an insufficient clearance of apoptotic debris. During apopt...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2010.08.003
更新日期：2010-11-01 00:00:00
abstract：:Major histocompatibility complex (MHC) molecules present peptide antigens to T lymphocytes and initiate immune responses. The peptides loaded onto MHC class I or MHC class II molecules can be derived from cytosolic proteins, both self and foreign. A variety of cellular processes, including endocytosis, vesicle traffic...
journal_title：Molecular immunology
pub_type： 杂志文章,评审
doi：10.1016/j.molimm.2018.05.009
更新日期：2018-07-01 00:00:00
abstract：:Effective immunization with short polypeptide antigens has typically only been possible when the peptide is conjugated to a large carrier substance, usually a protein. Such immunizations suffer from difficulties in producing conjugates of reliable composition, and from unwanted anti-carrier immune responses. When a ch...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(84)90084-1
更新日期：1984-01-01 00:00:00
abstract：:Leucine-rich repeat-containing G-protein-coupled receptors (LGRs) form a subfamily of the large superfamily of G-protein-coupled receptors. LGRs can be divided into three groups. LGR2 from Drosophila melanogaster is involved in cuticle tanning (melanization and sclerotization). In this study, one LGR2 (MnLGR2) was ide...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2020.07.013
更新日期：2020-10-01 00:00:00
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journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2006.05.010
更新日期：2007-02-01 00:00:00
abstract：:Very sensitive assays of IgE are required for determining prevalence of allergic reactions in children. In order to develop a sensitive two-site IRMA two kinds of mAb were produced. Antibodies specific for D epsilon 1 determinants were derived from immunization with a 40 kDa papain Fc fragment. They bound equally nati...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(87)90158-1
更新日期：1987-11-01 00:00:00
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journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2020.03.021
更新日期：2020-04-16 00:00:00
abstract：:Chagas' disease, caused by Trypanosoma cruzi, is an inflammatory disorder leading to chronic Chagas cardiomyopathy (CCC). Only one third of T. cruzi-infected individuals progress to CCC while the others are considered asymptomatic (ASY). The human inhibitory kappaB-like gene (IKBL/NFKBIL1), homologous to the IkappaB f...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2007.04.015
更新日期：2008-01-01 00:00:00
abstract：:Lewis (LEW) and Wistar Kyoto (WKY) rats of the same major histocompatibility complex (MHC) haplotype (RT.1(l)) display differential susceptibility to adjuvant-induced arthritis (AIA). LEW are susceptible while WKY are resistant to AIA. To gain insights into the mechanistic basis of these disparate outcomes, we compare...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2013.05.230
更新日期：2013-12-01 00:00:00
abstract：:Pathogenic fungi represent a major threat particularly to immunocompromised hosts, leading to severe, and often lethal, systemic opportunistic infections. Although the impaired immune status of the host is clearly the most important factor leading to disease, virulence factors of the fungus also play a role. Factor H ...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2007.08.011
更新日期：2008-03-01 00:00:00
abstract：:Artificial Salmonella serogroup B, D or Cl-specific glycolipids were prepared by covalently linking oligosaccharides corresponding to two O-antigen repeating units, obtained by phage enzyme hydrolysis of native O-antigenic polysaccharides, to octyl residues. Sheep erythrocytes coated with the artificial glycolipids we...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(90)90152-p
更新日期：1990-09-01 00:00:00
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journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2009.07.001
更新日期：2009-09-01 00:00:00
abstract：:Following measles virus (MV) infection, viral peptides are presented to CTL by MHC class I molecules on infected antigen presenting cells at widely different epitope densities. Whereas three MV epitopes (MV-M(211-219), MV-F(438-446) and MV-H(30-38)) derived from different structural proteins occur at regular densities...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/s0161-5890(02)00204-3
更新日期：2003-01-01 00:00:00
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journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(83)90139-6
更新日期：1983-11-01 00:00:00
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journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2008.01.009
更新日期：2008-05-01 00:00:00
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journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2005.07.030
更新日期：2006-03-01 00:00:00
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journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2019.09.005
更新日期：2019-10-01 00:00:00
abstract：:Emerging evidence has indicated that vascular endothelial cells (ECs) not only form the barrier between blood and the vessel wall but also serve as conditional innate immune cells. Our previous study found that SIRT1, a class III histone deacetylase, inhibits the inflammatory response in ECs. Recent studies revealed t...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2016.07.018
更新日期：2016-09-01 00:00:00
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journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(85)90052-5
更新日期：1985-12-01 00:00:00
abstract：:To investigate the IL-6/IL-6 receptor system, we obtained five murine monoclonal antibodies against human IL-6, which neutralize its biological activity. We classified them into two groups (Type I mAb and Type II mAb) according to the epitopes they recognized. These two types of antibodies showed no difference in the ...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(91)90001-z
更新日期：1991-11-01 00:00:00
abstract：:This study aimed to co-culture Jurkat T lymphocytes with inactivated Mycobacterium tuberculosis (Mtb H37Ra), explore whether T lymphocytes could phagocytose H37Ra cells, and determine the underlying mechanism. Jurkat T lymphocytes were co-cultured with H37Ra cells, and confocal laser scanning microscopy, electron micr...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2015.04.018
更新日期：2015-08-01 00:00:00
abstract：:Antimicrobial peptides (AMPs) are important components of the host's innate immune response against microbial invasion. The cysteine-rich AMPs such as defensin and hepcidin have been extensively studied, but the recently identified cysteine-rich liver-expressed antimicrobial peptide 2 (LEAP-2) has been characterized f...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2005.02.014
更新日期：2006-02-01 00:00:00
abstract：:The alternative pathway of complement is receiving increasing attention as a therapeutic target because of recent findings in several animal models that support its essential role in tissue injury and disease pathogenesis. Although the contribution of alternative pathway activation to serum complement activation in vi...
journal_title：Molecular immunology
pub_type： 杂志文章,评审
doi：10.1016/j.molimm.2004.03.012
更新日期：2004-06-01 00:00:00
abstract：:A monoclonal human IgG1, Campath-1H, was digested with glycosidases to assess the effect of carbohydrate on the functional activities of an IgG1. Removal of the complete carbohydrate moiety abolished complement lysis activity and antibody-dependent cell-mediated cytotoxicity, but left antigen binding activity and prot...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(95)00118-2
更新日期：1995-12-01 00:00:00
abstract：:Peptide fragments of pertussis toxin subunit 1 (PT-S1) have been synthesized in order to investigate their antigenic and immunogenic activity, and to evaluate their possible use as components of a new vaccine. Two peptides (sequence 73-82, EAERAGRGTG and sequence 107-116, YVDTYGDNAG) were selected for their predictabl...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(89)90025-4
更新日期：1989-01-01 00:00:00
abstract：:A procedure to quantitate the immunogenic potential of protein antigens is presented. It is hypothesized that the intrinsic immunogenicity of an accessible region on the protein arises from the overall structural effect of the presence of the particular assemblage of amino acid residues in the given region. Structural...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/0161-5890(85)90043-4
更新日期：1985-11-01 00:00:00
abstract：:Polyclonal or monoclonal human IgM rheumatoid factors (RF) react with eight antigenic sites on the CH3 IgG domain, four sites on CH2 and two on human beta 2-microglobulin. All 14 of these RF-reactive epitopes are linear 7-11 amino acid peptides with different primary sequence. We questioned whether RF reactivity with ...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/s0161-5890(97)00024-2
更新日期：1997-05-01 00:00:00
abstract：:We showed that nucleotide sequences coding for linear B-cell epitopes of human immunodeficiency virus type 1 (HIV1) gp120 protein are enriched with codons containing cytosine and guanine in their first and second codon positions. Guanine and cytosine are the most mutable nucleotides in HIV1 genes (due to APOBEC3 and A...
journal_title：Molecular immunology
pub_type： 杂志文章
doi：10.1016/j.molimm.2010.01.006
更新日期：2010-04-01 00:00:00
