© The Rockefeller University Press, 0022-1007/1997/11/1419/ $5.00
The Journal of Experimental Medicine, Volume 186, Number 9, November 3, 1997 1419-1429
Molecular Characterization and Functional Analysis of Murine Interleukin 4 Receptor Allotypes
T. Schulte*,
R. Kurrle
,
M. Röllinghoff*, and
A. Gessner*
From the * Institute of Clinical Microbiology and Immunology, University of Erlangen-Nürnberg, 91054 Erlangen, Germany; and
Behringwerke AG, 35001 Marburg, Germany
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.
Address correspondence to Dr. André Gessner, Institute of Clinical Microbiology and Immunology, Wasserturmstr. 3, 91054 Erlangen, Germany. Phone: 49-9131-852-580; FAX: 49-9131-852-573; E-mail: gessner{at}mikrobio.med.uni-erlangen.de
1 Abbreviations used in this paper: EAE, experimental allergic encephalomyelitis; s, soluble.

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