Novel immunoglobuline-like transcripts in teleost fish encode polymorphic receptors with cytoplasmic ITAM and ITIM and a new structural Ig domain similar to the natural cytotoxicity receptor NKp44.

Rene Josephus Maria Stet, T. T. Hermsen, A. H. Westphal, J. Jukes, M. Engelsma, B. M. L. Verburg-van Kemenade, J. Dortmans, J. Aveiro, H. F. J. Savelkoul

    Research output: Contribution to journalArticle

    41 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)77-89
    Number of pages12
    JournalImmunogenetics
    Volume57
    DOIs
    Publication statusPublished - 2005

    Keywords

    • fish leucocyte receptor
    • NKp44
    • TREM
    • ITAM
    • ITIM
    • CARP CYPRINUS-CARPIO
    • TUMOR-CELL LYSIS
    • GENE FAMILY
    • FUNCTIONAL-CHARACTERIZATION
    • HISTOCOMPATIBILITY COMPLEX
    • KILLER-CELLS
    • ZEBRAFISH
    • CLUSTER
    • MEMBER
    • CONSERVATION

    Cite this

    Novel immunoglobuline-like transcripts in teleost fish encode polymorphic receptors with cytoplasmic ITAM and ITIM and a new structural Ig domain similar to the natural cytotoxicity receptor NKp44. / Stet, Rene Josephus Maria; Hermsen, T. T.; Westphal, A. H.; Jukes, J.; Engelsma, M.; Verburg-van Kemenade, B. M. L.; Dortmans, J.; Aveiro, J.; Savelkoul, H. F. J.

    In: Immunogenetics, Vol. 57, 2005, p. 77-89.

    Research output: Contribution to journalArticle

    Stet, Rene Josephus Maria ; Hermsen, T. T. ; Westphal, A. H. ; Jukes, J. ; Engelsma, M. ; Verburg-van Kemenade, B. M. L. ; Dortmans, J. ; Aveiro, J. ; Savelkoul, H. F. J. / Novel immunoglobuline-like transcripts in teleost fish encode polymorphic receptors with cytoplasmic ITAM and ITIM and a new structural Ig domain similar to the natural cytotoxicity receptor NKp44. In: Immunogenetics. 2005 ; Vol. 57. pp. 77-89.
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    abstract = "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.",
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    T1 - Novel immunoglobuline-like transcripts in teleost fish encode polymorphic receptors with cytoplasmic ITAM and ITIM and a new structural Ig domain similar to the natural cytotoxicity receptor NKp44.

    AU - Stet, Rene Josephus Maria

    AU - Hermsen, T. T.

    AU - Westphal, A. H.

    AU - Jukes, J.

    AU - Engelsma, M.

    AU - Verburg-van Kemenade, B. M. L.

    AU - Dortmans, J.

    AU - Aveiro, J.

    AU - Savelkoul, H. F. J.

    PY - 2005

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    AB - 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.

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    KW - ITAM

    KW - ITIM

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    KW - TUMOR-CELL LYSIS

    KW - GENE FAMILY

    KW - FUNCTIONAL-CHARACTERIZATION

    KW - HISTOCOMPATIBILITY COMPLEX

    KW - KILLER-CELLS

    KW - ZEBRAFISH

    KW - CLUSTER

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    KW - CONSERVATION

    U2 - 10.1007/s00251-005-0771-9

    DO - 10.1007/s00251-005-0771-9

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