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Identification of a gene for an ancient cytokine, interleukin 15-like, in mammals; interleukins 2 and 15 co-evolved with this third family member, all sharing binding motifs for IL-15Rα

Dijkstra,JM, Takizawa,F, Fischer,U, Friedrich,M, Soto-Lampe,V, Lefèvre,C, Lenk,M, Karger,A, Matsui,T and Hashimoto,K 2014, Identification of a gene for an ancient cytokine, interleukin 15-like, in mammals; interleukins 2 and 15 co-evolved with this third family member, all sharing binding motifs for IL-15Rα, Immunogenetics, vol. 66, no. 2, pp. 93-103, doi: 10.1007/s00251-013-0747-0.

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Title Identification of a gene for an ancient cytokine, interleukin 15-like, in mammals; interleukins 2 and 15 co-evolved with this third family member, all sharing binding motifs for IL-15Rα
Author(s) Dijkstra,JM
Takizawa,F
Fischer,U
Friedrich,M
Soto-Lampe,V
Lefèvre,C
Lenk,M
Karger,A
Matsui,T
Hashimoto,K
Journal name Immunogenetics
Volume number 66
Issue number 2
Start page 93
End page 103
Publisher Springer
Place of publication Heidelberg, Germany
Publication date 2014-02
ISSN 1432-1211
Keyword(s) 15 and 15-like
Cytokine
Evolution
Interleukins 2
Receptor
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
Immunology
TROUT ONCORHYNCHUS-MYKISS
CD4(+) T-CELLS
CRYSTAL-STRUCTURE
FUNCTIONAL-CHARACTERIZATION
RECEPTOR-ALPHA
JAPANESE PUFFERFISH
EXPRESSION ANALYSIS
HELICAL CYTOKINES
IL-2 RECEPTOR
GAMMA-CHAIN
Summary Interleukins 2 and 15 (IL-2 and IL-15) are highly differentiated but related cytokines with overlapping, yet also distinct functions, and established benefits for medical drug use. The present study identified a gene for an ancient third IL-2/15 family member in reptiles and mammals, interleukin 15-like (IL-15L), which hitherto was only reported in fish. IL-15L genes with intact open reading frames (ORFs) and evidence of transcription, and a recent past of purifying selection, were found for cattle, horse, sheep, pig and rabbit. In human and mouse the IL-15L ORF is incapacitated. Although deduced IL-15L proteins share only ~21 % overall amino acid identity with IL-15, they share many of the IL-15 residues important for binding to receptor chain IL-15Rα, and recombinant bovine IL-15L was shown to interact with IL-15Rα indeed. Comparison of sequence motifs indicates that capacity for binding IL-15Rα is an ancestral characteristic of the IL-2/15/15L family, in accordance with a recent study which showed that in fish both IL-2 and IL-15 can bind IL-15Rα. Evidence reveals that the species lineage leading to mammals started out with three similar cytokines IL-2, IL-15 and IL-15L, and that later in evolution (1) IL-2 and IL-2Rα receptor chain acquired a new and specific binding mode and (2) IL-15L was lost in several but not all groups of mammals. The present study forms an important step forward in understanding this potent family of cytokines, and may help to improve future strategies for their application in veterinarian and human medicine.
Language eng
DOI 10.1007/s00251-013-0747-0
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 929999 Health not elsewhere classified
HERDC Research category C1 Refereed article in a scholarly journal
ERA Research output type C Journal article
Copyright notice ©2014, Springer
Persistent URL http://hdl.handle.net/10536/DRO/DU:30072840

Document type: Journal Article
Collections: School of Medicine
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Every reasonable effort has been made to ensure that permission has been obtained for items included in DRO. If you believe that your rights have been infringed by this repository, please contact drosupport@deakin.edu.au.