A monoclonal antibody directed against an autoimmune epitope on the human beta1-adrenergic receptor recognized in idiopathic dilated cardiomyopathy.

• A monoclonal antibody (MAb M16) was obtained by immunizing Balb/C mice with free peptide H26R, corresponding to the second extracellular loop of the human beta1-adrenergic receptor (beta1AR), against which functional autoantibodies have been detected in patients with idiopathic dilated cardiomyopathy. The MAb was found to be of IgG2b type and directed against a conformational epitope, encompassing the sequence recognized by the human autoantibodies. BIAcore measurements yielded an equilibrium constant of 6.5 X 10(7) M1 with an association rate constant (kon) of 6.5 X 10(4) M(-1) sec(-1) and a dissociation rate constant (koff) of 1.0 X 10(-3) sec(-1). It immunoprecipitated only poorly the solubilized beta1AR of Sf9 cell membranes. Functionally, the MAb was capable of not only reducing the number of the maximal binding sites to the beta1-adrenergic receptor of transfected Sf9 cell membranes, but also of displaying a positive chronotropic effect on cultured neonatal rat cardiomyocytes. These properties, which the MAb shares with the human autoantibodies, makes it an interesting tool for passive transfer studies in mice.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Fysiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Physiology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Microbiology in the medical area (hsv//eng)

Keyword

Amino Acid Sequence

Animals

Animals

Newborn

Antibodies

Monoclonal

chemistry

immunology

Antibody Affinity

Autoantigens

immunology

Cardiomyopathy

Dilated

immunology

Cells

Cultured

Epitope Mapping

Heart Rate

Humans

Hybridomas

Immunoglobulin G

analysis

Mice

Mice

Inbred BALB C

immunology

Molecular Sequence Data

Myocardium

cytology

Peptides

immunology

Precipitin Tests

Rats

Rats

Wistar

Receptors

Adrenergic

beta-1

genetics

immunology

Spodoptera

genetics

Transfection

Publication and Content Type

ref (subject category)

art (subject category)