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ARS Home » Southeast Area » Stoneville, Mississippi » Warmwater Aquaculture Research Unit » Research » Publications at this Location » Publication #418963
Research Project: Improving the Productivity and Quality of Catfish Aquaculture

Location: Warmwater Aquaculture Research Unit

Title: Extraordinary diversity of the CD28/CTLA4 family across jawed vertebrates

Author
item Quiniou, Sylvie
item CLARK, THOMAS - University Of Edinburgh
item BENGTEN, EVA - University Of Mississippi Medical Center
item RAST, JOHN - Emory University, School Of Medicine
item OHTA, YUKO - University Of Maryland School Of Medicine
item FLAJNIK, MARTIN - University Of Maryland School Of Medicine
item BOUDINOT, PIERRE - Inrae

Submitted to: Frontiers in Immunology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/27/2024
Publication Date: 11/12/2024
Citation: Quiniou, S., Clark, T., Bengten, E., Rast, J., Ohta, Y., Flajnik, M., Boudinot, P. 2024. Extraordinary diversity of the CD28/CTLA4 family across jawed vertebrates. Frontiers in Immunology. 15. https://doi.org/10.3389/fimmu.2024.1501934.
DOI: https://doi.org/10.3389/fimmu.2024.1501934

Interpretive Summary: Members of the CD28 family of receptors are critical for the control of immune cell activation in fish as in human. Using genomics ressources, we found counterparts of all members of the CD28 family both in sharks and rays as well as in bony fish, but not in lampreys and hagfish. Four new members of the family were identified, which were present in both sharks and bony fish, some even reptiles or some mammals but all of them absent in human. Herein, we extend the composition of the vertebrate CD28 family to nine members: CD28, CTLA4, ICOS, CD28H, CD28HL1, CD28HL2, CD28HL3, CD28X and PD-1. Our findings show that a large diversification of these co-stimulatory/co-inhibitory receptors arose early in vertebrate evolution, and that the regulation of fish immune response to vaccines and pathogens is more complex than previously thought.

Technical Abstract: Members of the CD28 family are critical for the control of immune cell activation. While CD28 and CTLA4 were previously identified in teleost fish, most members of the CD28 family have been described only in tetrapods. Using a comparative genomics approach, we found (co)orthologs of all members of the CD28 family both in Chondrichtyes and basal Osteichtyes groups, but not in Agnathans. Four additional members of the family were identified, which were present in both Chondrichtyes and Osteichtyes, some even in the tetrapod lineage but all of them absent in human. Herein, we extend the composition of the jawed vertebrate CD28 family to nine members: CD28, CTLA4, ICOS, CD28H, CD28HL1, CD28HL2, CD28HL3, CD28X and PD-1. Each of these genes had a single extracellular IgSF V domain, and conserved motifs in the V and the cytoplasmic domain. While a genomic cluster of three consecutive genes like CD28/CTLA4/ICOS was conserved across jawed vertebrates except in teleosts, the other members of the CD28 family were located on multiple chromosomes. Our findings show that a large diversification of these co-stimulatory/co-inhibitory receptors arose when the Ig/ TCR/MHC-based adaptive immunity emerged in early jawed vertebrates, heralding the advent of complex regulatory networks controlling lymphocyte activation.