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ARS Home » Southeast Area » Stoneville, Mississippi » Warmwater Aquaculture Research Unit » Research » Publications at this Location » Publication #408823
Research Project: Improving the Productivity and Quality of Catfish Aquaculture

Location: Warmwater Aquaculture Research Unit

Title: Costimulatory receptors in the Channel catfish: CD28 family members and their ligands

Author
item Quiniou, Sylvie
item BENGTEN, EVA - University Of Mississippi Medical Center
item BOUDINOT, PIERRE - Inrae

Submitted to: Immunogenetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/10/2023
Publication Date: 1/10/2024
Citation: Quiniou, S., Bengten, E., Boudinot, P. 2024. Costimulatory receptors in the Channel catfish: CD28 family members and their ligands . Immunogenetics. 76:51-67. https://doi.org/10.1007/s00251-023-01327-3.
DOI: https://doi.org/10.1007/s00251-023-01327-3

Interpretive Summary: T cells are white blood cells essential for immune responses against pathogens, in fish as well as in humans. Their activation needs to be tightly controlled to avoid excessive aggression leading to self-destruction of the body by this defense system. We identified and characterized the repertoire of key Channel catfish genes controlling T cell activation, and their evolution from fish to human. These critical genes controlling the response of channel catfish to pathogens like viruses and bacteria constitute important targets for genetic selection promoting robustness and resistance to infections. These results also shed light on the respective contribution of the human gene counterparts which are critical target of antitumoral drug development.

Technical Abstract: The CD28/B7 axis is required to deliver a second signal required for T-cell activation. Membrane receptors belonging to CD28 and B7 families are involved in immune checkpoints that regulate positively or negatively leukocyte activation, in particular T lymphocytes. BTLA is an inhibitory receptor which belongs to a third family. Fish orthologs exist only for some of these genes, and the potential interactions between the corresponding receptors remain mostly unclear. In this work, we focused on the Channel catfish (Ictalurus punctatus), a leading species in world aquaculture and a long-standing model for fish immunology, to analyze these co-stimulatory/inhibitory receptors. We identified one copy of cd28, CTLA-4, cd80/86, b7h1/dc, b7h3, b7h4, b7h5, two btla, and 4 b7h7 genes. Catfish CD28 contains the same highly conserved cytoplasmic motif of PI3K and GRB2 recruitment as in mammals, but are absent in cyprinids, while CTLA-4 has a C terminal putative Grb2-binding site shared with other fish sequences only. Fish CD80/86 do not have a conserved ligand-binding patch in its V domain, but the C domain residues involved in the binding are highly conserved, suggesting they are important. Catfish B7H1 had a long intracytoplasmic domain with a P-loop-NTPase domain that is absent from mammalian sequences, while the lack of NLS in fish B7H4 suggests this protein may not promote cell growth when expressed intracellularly. Finally, there is a notable expansion of fish B7H7s, which likely plays diverse roles in leukocyte activation. Overall, our work contributes to a better understanding of fish leukocyte co-stimulatory and co-inhibitory receptors.