Probing the immunological properties of the extracellular domains of the human beta(1)-adrenoceptor.

• The human beta(1)-adrenoceptor is an immune target for autoantibodies with functional activity in cardiovascular diseases. Different epitopes on the extracellular domains of the receptor are involved. To study the immunological and pharmacological properties of these epitopes, rabbits were immunized with peptides corresponding to a large domain in the N-terminal part of the receptor and to its first and second extracellular loops. In contrast to the two other peptides, the first extracellular loop did not have immunogenic properties but acted as a hapten. Antibodies affinity-purified with the three synthetic peptides were able to significantly immunoprecipitate the solubilized receptor, confirming that they recognized the target receptor. While antibodies against the N-terminal domain did not inhibit the binding of a radiolabelled antagonist to the receptor, those against the first and second extracellular loop showed non-competitive inhibition. Similarly, only the two latter antibodies exerted a specific agonist-like effect on the receptor, as assessed on neonatal rat cardiomyocytes in culture. Our results are in accordance with those found for human anti-receptor autoantibodies with functional effects. We conclude that not all extracellular epitopes give rise to functional autoantibodies with potential physiopathological relevance in cardiac diseases with an autoimmune component.

Subject headings

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

Adrenergic beta-Agonists

Amino Acid Sequence

Animals

Animals

Newborn

Antibody Specificity

Autoantibodies

Cardiovascular Diseases

etiology

immunology

Cell Polarity

Cells

Cultured

Humans

Models

Molecular

Molecular Sequence Data

Myocardial Contraction

drug effects

Myocardium

cytology

Peptide Fragments

immunology

Rats

Receptors

Adrenergic

beta-1

immunology

T-Lymphocytes

immunology

Publication and Content Type

ref (subject category)

art (subject category)