Differential glycosylation of interleukin 2, the molecular basis for the NOD Idd3 type 1 diabetes gene?
The insulin-dependent diabetes (Idd) gene, Idd3, has been localised to a 0.35 cM region of chromosome 3 containing the structural gene for the cytokine interleukin 2 (IL-2). While variation of the N-terminal amino acid sequence of IL-2 has been shown to correlate with Idd3 allelic variation, differences in induction of proliferation by IL-2 allotypes have not been detected. In the current study, we examined the electrophoretic migration of IL-2 allotypes and have found two distinct patterns, consistent with differences in glycosylation, that correlate with diabetes-resistance and susceptibility. These findings strongly suggest that IL-2 variants may be functionally distinct.
Podolin
P L
PL
Department of Autoimmune Diseases Research, Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Wilusz
M B
MB
Cubbon
R M
RM
Pajvani
U
U
Lord
C J
CJ
Todd
J A
JA
Peterson
L B
LB
Wicker
L S
LS
Lyons
P A
PA
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000276:immunology; D004591:Electrophoresis, Polyacrylamide Gel; D006031:Glycosylation; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data
D007376:Interleukin-2