Genetic and Functional Diversity of Allorecognition Receptors in the Urochordate,

Overview

Journal bioRxiv

Date 2024 Oct 28

PMID 39463968

Authors

Henry Rodriguez-Valbuena

Jorge Salcedo

Olivier De Their

Jean Francois Flot

Stefano Tiozzo

Anthony W De Tomaso

Affiliations

Soon will be listed here.

Abstract

Allorecognition in is controlled by a highly polymorphic locus (the ), and functionally similar to missing-self recognition utilized by Natural Killer cells-compatibility is determined by sharing a self-allele, and integration of activating and inhibitory signals determines outcome. We had found these signals were generated by two -encoded receptors, called and Here we show that genes are members of an extended family consisting of >37 loci, and co-expressed with an even more diverse gene family-the (). The are membrane proteins related to , but include conserved tyrosine motifs, including ITIMs and hemITAMs. Both genes are encoded in highly polymorphic haplotypes on multiple chromosomes, revealing an unparalleled level of diversity of innate receptors. Our results also suggest that ITAM/ITIM signal integration is a deeply conserved mechanism that has allowed convergent evolution of innate and adaptive cell-based recognition systems.

References

Nei M, Gu X, Sitnikova T . Evolution by the birth-and-death process in multigene families of the vertebrate immune system. Proc Natl Acad Sci U S A. 1997; 94(15):7799-806. PMC: 33709. DOI: 10.1073/pnas.94.15.7799. View

Nicotra M . Invertebrate allorecognition. Curr Biol. 2019; 29(11):R463-R467. DOI: 10.1016/j.cub.2019.03.039. View

Grabherr M, Haas B, Yassour M, Levin J, Thompson D, Amit I . Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nat Biotechnol. 2011; 29(7):644-52. PMC: 3571712. DOI: 10.1038/nbt.1883. View

Blanchoud S, Rutherford K, Zondag L, Gemmell N, Wilson M . De novo draft assembly of the Botrylloides leachii genome provides further insight into tunicate evolution. Sci Rep. 2018; 8(1):5518. PMC: 5882950. DOI: 10.1038/s41598-018-23749-w. View

Madeira F, Madhusoodanan N, Lee J, Eusebi A, Niewielska A, Tivey A . The EMBL-EBI Job Dispatcher sequence analysis tools framework in 2024. Nucleic Acids Res. 2024; 52(W1):W521-W525. PMC: 11223882. DOI: 10.1093/nar/gkae241. View

Kelley J, Walter L, Trowsdale J . Comparative genomics of natural killer cell receptor gene clusters. PLoS Genet. 2005; 1(2):129-39. PMC: 1193534. DOI: 10.1371/journal.pgen.0010027. View

Carlyle J, Mesci A, Fine J, Chen P, Belanger S, Tai L . Evolution of the Ly49 and Nkrp1 recognition systems. Semin Immunol. 2008; 20(6):321-30. DOI: 10.1016/j.smim.2008.05.004. View

Stefanova I, Hemmer B, Vergelli M, Martin R, Biddison W, Germain R . TCR ligand discrimination is enforced by competing ERK positive and SHP-1 negative feedback pathways. Nat Immunol. 2003; 4(3):248-54. DOI: 10.1038/ni895. View

Sibener L, Fernandes R, Kolawole E, Carbone C, Liu F, McAffee D . Isolation of a Structural Mechanism for Uncoupling T Cell Receptor Signaling from Peptide-MHC Binding. Cell. 2018; 174(3):672-687.e27. PMC: 6140336. DOI: 10.1016/j.cell.2018.06.017. View

10.

Obenauer J, Cantley L, Yaffe M . Scansite 2.0: Proteome-wide prediction of cell signaling interactions using short sequence motifs. Nucleic Acids Res. 2003; 31(13):3635-41. PMC: 168990. DOI: 10.1093/nar/gkg584. View

11.

Ashby K, Hogquist K . A guide to thymic selection of T cells. Nat Rev Immunol. 2023; 24(2):103-117. DOI: 10.1038/s41577-023-00911-8. View

12.

Rodriguez D, Braden B, Boyer S, Taketa D, Setar L, Calhoun C . In vivo manipulation of the extracellular matrix induces vascular regression in a basal chordate. Mol Biol Cell. 2017; 28(14):1883-1893. PMC: 5541839. DOI: 10.1091/mbc.E17-01-0009. View

13.

Grice L, Gauthier M, Roper K, Fernandez-Busquets X, Degnan S, Degnan B . Origin and Evolution of the Sponge Aggregation Factor Gene Family. Mol Biol Evol. 2017; 34(5):1083-1099. PMC: 5400394. DOI: 10.1093/molbev/msx058. View

14.

Joncker N, Shifrin N, Delebecque F, Raulet D . Mature natural killer cells reset their responsiveness when exposed to an altered MHC environment. J Exp Med. 2010; 207(10):2065-72. PMC: 2947079. DOI: 10.1084/jem.20100570. View

15.

Shilling H, Young N, Guethlein L, Cheng N, Gardiner C, Tyan D . Genetic control of human NK cell repertoire. J Immunol. 2002; 169(1):239-47. DOI: 10.4049/jimmunol.169.1.239. View

16.

Karre K . Natural killer cell recognition of missing self. Nat Immunol. 2008; 9(5):477-80. DOI: 10.1038/ni0508-477. View

17.

Taketa D, Nydam M, Langenbacher A, Rodriguez D, Sanders E, De Tomaso A . Molecular evolution and in vitro characterization of Botryllus histocompatibility factor. Immunogenetics. 2015; 67(10):605-23. PMC: 11614195. DOI: 10.1007/s00251-015-0870-1. View

18.

Elliott J, Wahle J, Yokoyama W . MHC class I-deficient natural killer cells acquire a licensed phenotype after transfer into an MHC class I-sufficient environment. J Exp Med. 2010; 207(10):2073-9. PMC: 2947074. DOI: 10.1084/jem.20100986. View

19.

Nydam M, Hoang T, Shanley K, De Tomaso A . Molecular evolution of a polymorphic HSP40-like protein encoded in the histocompatibility locus of an invertebrate chordate. Dev Comp Immunol. 2013; 41(2):128-36. DOI: 10.1016/j.dci.2013.03.004. View

20.

Delsuc F, Brinkmann H, Chourrout D, Philippe H . Tunicates and not cephalochordates are the closest living relatives of vertebrates. Nature. 2006; 439(7079):965-8. DOI: 10.1038/nature04336. View