Generation and characterization of a human monoclonal autoantibody that acts as a high affinity interleukin-1 alpha specific inhibitor

Mol Immunol. 1996 May-Jun;33(7-8):649-58. doi: 10.1016/0161-5890(96)00017-x.


Interleukin-1 (IL-1) defines two polypeptides, IL-1 alpha and IL-1 beta, that possess a wide spectrum of biological effects. Two natural antagonists of IL-1 action have been characterized: the IL-1 receptor antagonist (IL-1Ra) and a soluble form of the type II IL-1 receptor. Neutralizing autoantibodies to IL-1 alpha have also been detected in sera of healthy individuals and patients with autoimmune or inflammatory diseases. To characterize such antibodies molecularly, we attempted to generate B cell clones producing anti-IL-1 alpha human monoclonal antibody (HuMAb) by combining Epstein-Barr virus-immortalization and CD40-activation of B lymphocytes from individuals with circulating anti-IL-1 alpha. We describe herein the generation and properties of a natural IgG4/kappa anti-IL-1 alpha monoclonal autoantibody, HuMAb X3, that bound specifically to human IL-1 alpha, but not to IL-1 beta and IL-1Ra, with a high affinity (Kd = 1.2 x 10(-10)M). HuMAb X3 inhibited IL-1 alpha binding to IL-1 receptors and neutralized biological activities of both recombinant and natural forms of IL-1 alpha. A recombinant form of HuMAb X3 was found to display identical specific IL-1 alpha antagonism. The presence of somatic mutations within X3 variable regions suggests an antigen-driven affinity maturation. This study extends the demonstration of the presence of high affinity neutralizing anti-IL-1 alpha autoantibodies that can function as a third type of IL-1 antagonist.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / biosynthesis*
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacology*
  • Antibody Affinity*
  • Antibody Specificity*
  • Autoantibodies / biosynthesis*
  • Autoantibodies / chemistry
  • Autoantibodies / pharmacology*
  • B-Lymphocytes / metabolism
  • Base Sequence
  • Binding, Competitive / immunology
  • Cell Line
  • Humans
  • Immunoglobulin Heavy Chains / genetics
  • Immunoglobulin Light Chains / genetics
  • Immunoglobulin Variable Region / genetics
  • Interleukin-1 / antagonists & inhibitors*
  • Interleukin-1 / immunology*
  • Lymphocyte Activation
  • Molecular Sequence Data
  • Mutation / immunology
  • Receptors, Interleukin-1 / antagonists & inhibitors
  • Receptors, Interleukin-1 / immunology
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology


  • Antibodies, Monoclonal
  • Autoantibodies
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Light Chains
  • Immunoglobulin Variable Region
  • Interleukin-1
  • Receptors, Interleukin-1
  • Recombinant Proteins