Biochemical Features of a Catalytic Antibody Light Chain, 22F6, Prepared from Human Lymphocytes

Hifumi, Emi; Fujimoto, Naoko; Arakawa, Mitsue; Saito, Eri; Matsumoto, Shingo; Kobayashi, Nobuyuki; Uda, Takaaki

doi:10.1074/jbc.m113.454579

Cited by 18 publications

(36 citation statements)

References 44 publications

(51 reference statements)

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“…The light chain hardly cleaved Arg (R)‐MCA (trypsin‐like substrate), Lys (K)‐MCA (amino peptidase‐like substrate), and Ala‐Pro‐Ala (APA)‐MCA (elastase‐like substrate). The velocities of QAR‐MCA, VPR‐MCA, EAR‐MCA, and EKK‐MCA were comparable with the values of 0.03 μM/h for the cleavage of Pro‐Phe‐Arg (PFR)‐MCA at a concentration of 0.7 μM L12 obtained by Smirnov et al (26) and 0.09 μM/h at a concentration of 4.0 μM 22F6 by Hifumi et al (28). The 23D4m seems to possess enzymatic features partly of trypsin and partly of factor Xa.…”

Section: Resultssupporting

confidence: 83%

“…2 A . The light‐chain 23D4m cleaved the peptide bond between Arg and MCA of Gln‐Ala‐Arg (QAR)‐MCA, which is mostly used as a trypsin‐like substrate, with a reaction velocity of 0.25 μM/h at a concentration of 5.0 μM 23D4m, whose value was 2 times greater than that of 22F6 catalytic light chain (wild‐type) (28). For Val‐Proline‐Arg (VPR)‐MCA (thrombin‐like substrate), Glu‐Ala‐Arg (EAR)‐MCA (factor Xa‐like substrate), and Glu‐Lys‐Lys (EKK)‐MCA (plasmin‐like substrate), it decomposed with a reaction velocity of 0.12, 0.09, and 0.05 μM/h, respectively.…”

Section: Resultsmentioning

confidence: 99%

“…We have already reported on the potential ability and advantages of human κ light‐chain germline genes belonging to subgroup II to effectively prepare a catalytic antibody. The germline gene A18b in subgroup II possesses His27d and/or His93, which can participate in a catalytic triad‐like structure (9, 28). Sharma et al (30) reported that their human κ light chain (A18b) was capable of cleaving TNF‐α and stated that the reactivity became different by the molecular form: dimeric or tetrameric.…”

Section: Discussionmentioning

confidence: 99%

“…Preparation of the 23D4 wild‐type gene was obtained in accordance with that described in reference (28). Briefly stated, peripheral blood lymphocytes were harvested from 100 ml peripheral blood obtained from a healthy volunteer immunized by previous infections of influenza viruses.…”

Section: Methodsmentioning

confidence: 99%

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Biochemical features and antiviral activity of a monomeric catalytic antibody light‐chain 23D4 against influenza A virus

et al. 2015

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Catalytic antibodies have exhibited interesting functions against some infectious viruses such as HIV, rabies virus, and influenza virus in vitro as well as in vivo. In some cases, a catalytic antibody light chain takes on several structures from the standpoint of molecular size (monomer, dimer, etc.) and/or isoelectronic point. In this study, we prepared a monomeric 23D4 light chain by mutating the C-terminal Cys to Ala of the wild-type. The mutated 23D4 molecule took a simple monomeric form, which could hydrolyze synthetic 4-methyl-coumaryl-7-amide substrates and a plasmid DNA. Because the monomeric 23D4 light chain suppressed the infection of influenza virus A/Hiroshima/37/2001 in an in vitro assay, the corresponding experiments were conducted in vivo, after the virus strain (which was taken from a human patient) was successfully adapted into BALB/cN Sea mice. In the experiments, a mixture of the monomeric 23D4 and the virus was nasally administered 1) with preincubation and 2) without preincubation. As a result, the monomeric 23D4 clearly exhibited the ability to suppress the influenza virus infection in both cases, indicating a potential drug for preventing infection of the influenza A virus.-Hifumi, E., Arakawa, M., Matsumoto, S., Yamamoto, T., Katayama, Y., Uda, T. Biochemical features and antiviral activity of a monomeric catalytic antibody light-chain 23D4 against influenza A virus. FASEB J. 29, 2347-2358 (2015). www.fasebj.org

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Section: Resultssupporting

confidence: 83%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Biochemical features and antiviral activity of a monomeric catalytic antibody light‐chain 23D4 against influenza A virus

et al. 2015

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“…Thus, this natural clearance of immune complexes can lower the deleterious secondary effects such as inflammation and infiltration of various molecules of the immune system. Catalytic antibodies are described both in physiology as well as under various pathological conditions, such as asthma, hemophilia A, multiple sclerosis, rheumatoid arthritis, Hashimoto's thyroiditis, sepsis, graft versus host disease in transplantation, and others (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). Depending on the target antigen, both pathogenic and beneficial role of catalytic antibodies have been described (10,19).…”

Section: Introductionmentioning

confidence: 99%

Catalytic antibodies in patients with systemic lupus erythematosus

Pradhan¹,

Pandit²,

Surve³

et al. 2018

Eur J Rheumatol

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Objective: Antibodies with catalytic (hydrolytic) properties to DNA or RNA have been reported in systemic lupus erythematosus (SLE). However, it is well known that ethnicity plays an important role in the presentation of SLE and severity of the disease; hence, these data may not truly represent a general feature of all SLE patients. Therefore, we have analyzed the hydrolyzing activity of immunoglobulin G (IgG) of SLE patients from the Indian population with an aim to decode whether the catalytic antibody response represents part of an active disease process. Methods: IgGs were isolated from the sera of 72 consecutive patients diagnosed with SLE. As a control, IgGs from healthy donors were used. The catalytic activity of IgG was measured by PFR-MCA and affinity-linked oligonucleotide nuclease assay. Results: IgGs from patients with SLE from the Indian subcontinent displayed significantly higher hydrolysis rates of both the surrogate substrate, PFR-MCA, and the DNA than IgG from healthy individuals. Intergroup comparisons of the IgG-PFR-MCA interactions with clinical manifestations of the disease demonstrated a significantly increased level of hydrolysis among the patients with renal involvement who tested positive for anti-dsDNA antibodies. The PFR-MCA hydrolysis also appears to be associated with the active disease (p=0.0988, vs. inactive group). Conclusion: The prevalence of catalytic antibodies represents a general feature of SLE patients, irrespective of their origin.

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Development of Lactobacillus paracasei harboring nucleic acid-hydrolyzing 3D8 scFv as a preventive probiotic against murine norovirus infection

Hoang

Cho

Kim

et al. 2014

Appl Microbiol Biotechnol

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The protein 3D8 single-chain variable fragment (3D8 scFv) has potential anti-viral activity due to its ability to penetrate into cells and hydrolyze nucleic acids. Probiotic Lactobacillus paracasei engineered to secrete 3D8 scFv for oral administration was used to test the anti-viral effects of 3D8 scFv against gastrointestinal virus infections. We found that injection of 3D8 scFv into the intestinal lumen resulted in the penetration of 3D8 scFv into the intestinal villi and lamina propria. 3D8 scFv secreted from engineered L. paracasei retained its cell-penetrating and nucleic acid-hydrolyzing activities, which were previously shown with 3D8 scFv expressed in Escherichia coli. Pretreatment of RAW264.7 cells with 3D8 scFv purified from L. paracasei prevented apoptosis induction by murine norovirus infection and decreased messenger RNA (mRNA) expression of the viral capsid protein VP1. In a mouse model, oral administration of the engineered L. paracasei prior to murine norovirus infection reduced the expression level of mRNA encoding viral polymerase. Taken together, these results suggest that L. paracasei secreting 3D8 scFv provides a basis for the development of ingestible anti-viral probiotics active against gastrointestinal viral infection.

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Biochemical Features of a Catalytic Antibody Light Chain, 22F6, Prepared from Human Lymphocytes

Cited by 18 publications

References 44 publications

Biochemical features and antiviral activity of a monomeric catalytic antibody light‐chain 23D4 against influenza A virus

Biochemical features and antiviral activity of a monomeric catalytic antibody light‐chain 23D4 against influenza A virus

Catalytic antibodies in patients with systemic lupus erythematosus

Development of Lactobacillus paracasei harboring nucleic acid-hydrolyzing 3D8 scFv as a preventive probiotic against murine norovirus infection

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