Molecular characterization and functional analysis of murine interleukin 4 receptor allotypes

J Exp Med. 1997 Nov 3;186(9):1419-29. doi: 10.1084/jem.186.9.1419.

Abstract

The murine interleukin 4 receptor (IL-4R) exists as a transmembrane protein transducing pleiotropic IL-4 functions, or as soluble (s)IL-4-binding molecule with potent immunoregulatory effects. In this study we identified and characterized a murine IL-4R allotype. Sequence analysis of the IL-4R cDNA of BALB/c mice revealed 18 base substitutions leading to three extracellular and five cytoplasmic amino acid changes when compared with the published IL-4R sequence of C57BL/6 mice. Analyses with allotype-specific mAbs revealed that AKR/J and SJL/J mice possess the newly identified BALB/c IL-4R allotype whereas the IL-4Rs of C3H, CBA, DBA-2, and FVB/N mice are identical to that of the C57BL/6 mouse. The extracellular Thr49 to Ile substitution abrogates one N-glycosylation site in the naturally occurring BALB/c IL-4R as well as in the experimentally point mutated C57BL/6-T49I sIL-4R, and both molecules display a nearly threefold reduction in IL-4-neutralizing activity compared to the C57BL/6 sIL-4R. In line with this, a significantly enhanced dissociation rate of IL-4 was detected for the BALB/c IL-4R allotype by surface plasmon resonance and in radioligand binding studies with IL-4R-transfected cell lines. These findings suggest that the altered ligand binding behavior of the newly described IL-4R allotype may influence the IL-4 responsiveness, thus contributing to the diverse phenotypes of inbred mouse strains in IL-4-dependent diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles*
  • Amino Acid Substitution / genetics
  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibody Specificity / genetics
  • Base Sequence
  • Binding Sites, Antibody / genetics
  • Cell Membrane / metabolism
  • DNA Restriction Enzymes
  • Epitope Mapping
  • Extracellular Space / chemistry
  • Extracellular Space / immunology
  • Female
  • Glycosylation
  • Kinetics
  • Mice
  • Mice, Inbred AKR
  • Mice, Inbred BALB C
  • Mice, Inbred C3H
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Mice, Inbred DBA
  • Mice, SCID
  • Receptors, Interleukin-4 / chemistry*
  • Receptors, Interleukin-4 / genetics*
  • Receptors, Interleukin-4 / immunology
  • Receptors, Interleukin-4 / metabolism

Substances

  • Antibodies, Monoclonal
  • Receptors, Interleukin-4
  • DNA Restriction Enzymes

Associated data

  • GENBANK/AF000304