Identification and characterization of two alternative splice variants of human interleukin-2.
Our previous work showed that alternative splicing is used to make an inhibitory variant of human interleukin (IL)-4. Because of homology between IL-4 and IL-2 proteins and receptors, we tested whether alternative splicing is used to generate similar inhibitory variants of human IL-2. Messenger RNA from peripheral blood mononuclear cells was subjected to reverse transcription-polymerase chain reaction using IL-2 exon 1- and exon 4-specific primers. Two amplification products, named IL-2delta2 and IL-2delta3, were found in addition to the native IL-2 product. The IL-2delta2 cDNA sequence was identical to IL-2 cDNA throughout the entire coding region, except exon 2 was omitted by alternative splicing. In IL-2delta3 cDNA, the third exon of IL-2 was omitted by alternative splicing. Unlike IL-2, IL-2delta2 and IL-2delta3 did not stimulate T cell proliferation. However, both inhibited IL-2 costimulation of T cell proliferation, and both inhibited cellular binding of rhIL-2 to high affinity IL-2 receptors. Thus, IL-2 is the second cytokine that uses alternative splicing to generate variants that are competitive inhibitors.
Tsytsikov
V N
VN
Division of Rheumatology & Clinical Immunology, Department of Medicine, University of Maryland at Baltimore, Baltimore, Maryland 21201, USA.
Yurovsky
V V
VV
Atamas
S P
SP
Alms
W J
WJ
White
B
B
D017398:Alternative Splicing; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D014644:Genetic Variation; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000037:antagonists & inhibitors*; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000187:drug effects
D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2