Immunodominant structures in the aminoterminal portion of human interferon α 1

Kontsek, Peter; Borecký, L; Kontseková, Eva; Kolcunova, Alexandra; Novák, Michal; Zav’yalov, V.P.; Maiorov, Valentin A.

doi:10.1016/0161-5890(92)90124-g

Cited by 23 publications

(4 citation statements)

References 17 publications

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“…(16)(17)(18) (11,17,(19)(20)(21)(22) and were used as hybridoma culture supernatants containing the respective antibodies at a concentration of 5-10 mg/ml.…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Amino Acid Substitutions in Loop BC and Helix C Affect Antigenic Properties of Helix D in Hybrid IFN-α21a/α2c Molecules

Schmeisser

Kontsek

et al. 2002

Journal of Interferon & Cytokine Research

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We compared the antigenic properties of human interferon-alpha2c (IFN-alpha2c), IFN-alpha21a, hybrids IFN-alpha21a/alpha2c, and their mutants, using a panel of 27 anti-IFN-alpha1, anti-IFN-alpha2, and anti-IFN-alpha8/1/8 monoclonal antibodies (mAb). After immunoanalysis by ELISA, we found parental IFN-alpha2c and IFN-alpha21a to be antigenically distinct. Lack of reactivity of anti-IFN-alpha1 mAb with IFN-alpha21a indicated an antigenic distinction between subtypes alpha1 and alpha21a. The antigenic properties of hybrid IFNs consisting of the N-terminal portion (1-75) of IFN-alpha21a and the C-terminal portion (76-166) of IFN-alpha2c were analyzed with mAb recognizing defined regions of IFN-alpha2c, IFN-alpha1, and IFN-alpha8/1/8. We found that extending the sequence of IFN-alpha21a up to position 95 in hybrid molecule decreased the immunoreactivity of mAb specific for the antigenic structure formed by residues --112-132-- (helix D) of IFN-alpha2c. Inserting the sequence 76-81 (loop BC) of IFN-alpha2c into the sequence of 1-95 of IFN-alpha21a restored the reactivity of anti-IFN-alpha2c mAb. Some amino acid substitutions at positions 86 and 90 (helix C) of hybrid IFN-alpha21a/alpha2c also affected the immunoreactivity of C-terminal-specific mAb, which recognize helix D, but did not influence the structure of C-terminus of IFN (aa 151-165). Changes in the structure of constructs affected not only their antiproliferative activity but also their antiviral activity on human cells.

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“…(16)(17)(18) (11,17,(19)(20)(21)(22) and were used as hybridoma culture supernatants containing the respective antibodies at a concentration of 5-10 mg/ml.…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Amino Acid Substitutions in Loop BC and Helix C Affect Antigenic Properties of Helix D in Hybrid IFN-α21a/α2c Molecules

Schmeisser

Kontsek

et al. 2002

Journal of Interferon & Cytokine Research

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“…The hybridoma NOAL 6/66.423.2, which produces mAb 423, has been described (1,23). The hybridoma NOAL 7.51 (mAb 7.51) was derived by using the spleen ofa BALB/c mouse hyperimmunized with the N11 subfraction as a source of cells for fusion with the NSO myeloma cell line, as described (27). NOAL 7.51 was selected on the basis of strong staining of normal human tau preparations and PHF core-derived tau fragments by immunodot assay.…”

Section: Methodsmentioning

confidence: 99%

Difference between the tau protein of Alzheimer paired helical filament core and normal tau revealed by epitope analysis of monoclonal antibodies 423 and 7.51.

Novák

Jakes

Edwards

et al. 1991

Proc. Natl. Acad. Sci. U.S.A.

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“…Monoclonal Antibodies. The following murine monoclonal antibodies were used: mAb N27 (epitope 43-53) against IFN-R2c (26), mAb NK2 (epitope 112-132) against human leukocyte IFN (27), mAb 1-36 (epitope 63-85) against human IFN-R1 (28), mAb 4F2 (epitope 113-149) against consensus IFN-R (9) and mAb III/21 against a synthetic fragment 151-165 of IFN-R1 (29). All antibodies have IFNneutralizing activity except mAb III/21, and were used as hybridoma culture supernatants containing respective antibodies at concentrations of 5-10 µg/mL.…”

Section: Methodsmentioning

confidence: 99%

Two Interferons Alpha Influence Each Other during Their Interaction with the Extracellular Domain of Human Type Interferon Receptor Subunit 2

et al. 2007

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The interaction between two human interferons alpha (IFN-αs) and the extracellular (EC) domain of human type I IFN receptor subunit 2 (IFNAR2) was analyzed. Previous experiments using Daudi cells showed that IFN-α21b and some IFN-α hybrids (made from IFN-α2c and 21b) competed poorly for the IFN-α2b binding site. This study examined the causes of the poor competition between these IFN-αs. IFN-α2c and the IFN hybrid CM3 {IFN-α21b(1-75)(81-95)/IFN-α2c(76-80)(96-166), Y86K} were selected for this study based on their cell binding and biological properties. Competitive binding ELISA, native electrophoresis followed by Western blot, electrospray ionization mass spectrometry (ESI-MS), surface plasmon resonance biosensor (SPR) analysis, as well as neutralization of antiproliferative activities on Daudi cells in the presence of soluble IFNAR2-EC show evidence that each of the described IFN-α subtypes affected the binding of the other IFN-α to IFNAR2-EC by affecting the stability of the complex, i.e. dissociation of the complex. Moreover, native electrophoresis with different IFNAR2-EC mutants showed that IFN-α2c and CM3 utilize different amino acids in the binding domain of IFNAR2-EC. In addition to that, analytical ultracentrifugation (AUC) revealed differences in the oligomeric state of the two studied interferons. Our results demonstrated that two individual IFN-αs interact differentially with IFNAR2-EC and influence each other during this interaction. This study contributes to the understanding of the mutual interaction between multiple IFN-α subtypes during the competition for binding to the receptor.In mammals, the type I IFNs are grouped into five major classes: α, β, ε, κ, ω (1,2,3). They are induced in all nucleated cells in response to viral and bacterial infections, natural and synthetic double-stranded RNA, mitogens, protozoa and certain cytokines (3,4).Human IFN-α is represented by a group of related subtypes, encoded by a multigene family comprising 14 non-allelic genes. At the protein level, there is 75%-99% identity in the primary structure of human IFN-α species (5,6,7). Individual subtypes show quantitatively distinct spectra of antiviral, antiproliferative and immunomodulatory activities (8,9,10,11). The existence of the numerous subtypes of IFN-α may provide a fine mechanism of regulating the biological effect of IFN.

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Immunodominant structures in the aminoterminal portion of human interferon α 1

Cited by 23 publications

References 17 publications

Amino Acid Substitutions in Loop BC and Helix C Affect Antigenic Properties of Helix D in Hybrid IFN-α21a/α2c Molecules

Amino Acid Substitutions in Loop BC and Helix C Affect Antigenic Properties of Helix D in Hybrid IFN-α21a/α2c Molecules

Difference between the tau protein of Alzheimer paired helical filament core and normal tau revealed by epitope analysis of monoclonal antibodies 423 and 7.51.

Two Interferons Alpha Influence Each Other during Their Interaction with the Extracellular Domain of Human Type Interferon Receptor Subunit 2

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