Novel immunoglobulin-like transcripts in teleost fish encode polymorphic receptors with cytoplasmic ITAM or ITIM and a new structural Ig domain similar to the natural cytotoxicity receptor NKp44.
Members of the immunoglobulin superfamily (IgSF) include a group of innate immune receptors located in the leukocyte receptor complex (LRC) and other small clusters such as the TREM/NKp44 cluster. These receptors are characterised by the presence of immunoglobulin domains, a stalk, a transmembrane domain, and a cytoplasmic region containing either an immunoreceptor tyrosine-based inhibitory motif (ITIM) or are linked to an adapter molecule with an activation motif (ITAM) for downstream signalling. We have isolated two carp cDNA sequences encoding receptors in which the extracellular Ig domain structurally resembles the novel V-type Ig domain of NKp44. This is supported by a homology model. The cytoplasmic regions contain either an ITAM (Cyca-NILT1) or ITIMs (Cyca-NILT2). The tissue expression of these receptors is nearly identical, with the highest expression in the immunological organs. Peripheral blood leucocytes showed no detectable expression, but upon in vitro culture expressed NILT1, the activating receptor, and not the inhibitory NILT2 receptor. Southern blot analysis indicated that the NILT1 and NILT2 sequences belong to a multigene family. Analysis of the NILT Ig domain-encoding sequences amplified from both genomic DNA and cDNA revealed extensive haplotypic and allelic polymorphism. Database mining of the zebrafish genome identified several homologs on Chromosome 1, which also contains a cluster of class I major histocompatibility genes. This constellation is reminiscent of the TREM/NKp44 gene cluster and the HLA complex located on human Chromosome 6. The carp NILT genes form a unique cluster of innate immune receptors, which are highly polymorphic, and characterised by a new Ig structural subfamily and are distinct from the novel immune-type receptors (Nitrs) found in other fish species.
Stet
René J M
RJ
Cell Biology and Immunology Group, Wageningen Institute of Animal Sciences, Wageningen University, Wageningen, The Netherlands. rene.stet@wur.nl
Hermsen
Trudi
T
Westphal
Adrie H
AH
Jukes
Jojanneke
J
Engelsma
Marc
M
Lidy Verburg-van Kemenade
B M
BM
Dortmans
Jos
J
Aveiro
Joao
J
Savelkoul
Huub F J
HF
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002347:Carps / Q000235:genetics* / Q000276:immunology; D002460:Cell Line; D030562:Databases, Protein; D007136:Immunoglobulins / Q000737:chemistry*; D008969:Molecular Sequence Data; D005810:Multigene Family; D055629:Natural Cytotoxicity Triggering Receptor 2; D009419:Nerve Tissue Proteins / Q000235:genetics; D011110:Polymorphism, Genetic; D011487:Protein Conformation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2; D011956:Receptors, Cell Surface / Q000235:genetics; D011971:Receptors, Immunologic / Q000737:chemistry* / Q000235:genetics*; D014158:Transcription, Genetic
D007136:Immunoglobulins; C112837:NCR2 protein, human; D055629:Natural Cytotoxicity Triggering Receptor 2; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C516772:PTPRF protein, human; D017027:Protein Tyrosine Phosphatases; D054623:Receptor-Like Protein Tyrosine Phosphatases, Class 2