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Molecular and Functional Analyses of the Primordial Costimulatory Molecule CD80/86 and Its Receptors CD28 and CD152 (CTLA-4) in a Teleost Fish
The moderate activation of T cells in mammals requires the costimulatory molecules, CD80 and CD86, on antigen-presenting cells to interact with their respective T cell receptors, CD28 and CD152 (CTLA-4), to promote costimulatory signals. In contrast, teleost fish (except salmonids) only possess CD80...
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Published in: | Frontiers in immunology 2022-06, Vol.13, p.885005-885005 |
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Main Authors: | , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The moderate activation of T cells in mammals requires the costimulatory molecules, CD80 and CD86, on antigen-presenting cells to interact with their respective T cell receptors, CD28 and CD152 (CTLA-4), to promote costimulatory signals. In contrast, teleost fish (except salmonids) only possess CD80/86 as their sole primordial costimulatory molecule. However, the mechanism, which underlies the interaction between CD80/86 and its receptors CD28 and CD152 still requires elucidation. In this study, we cloned and identified the
CD80/86
,
CD28
, and
CD152
genes of the grass carp (
Ctenopharyngodon idella
). The mRNA expression analysis showed that
CD80/86
,
CD28
, and
CD152
were constitutively expressed in various tissues. Further analysis revealed that
CD80/86
was highly expressed in IgM
+
B cells. Conversely,
CD28
and
CD152
were highly expressed in CD4
+
and CD8
+
T cells. Subcellular localization illustrated that CD80/86, CD28, and CD152 are all located on the cell membrane. A yeast two-hybrid assay exhibited that CD80/86 can bind with both CD28 and CD152.
In vivo
assay showed that the expression of
CD80/86
was rapidly upregulated in
Aeromonas hydrophila
infected fish compared to the control fish. However, the expression of
CD28
and
CD152
presented the inverse trend, suggesting that teleost fish may regulate T cell activation through the differential expression of CD28 and CD152. Importantly, we discovered that T cells were more likely to be activated by
A. hydrophila
after CD152 was blocked by anti-CD152 antibodies. This suggests that the teleost CD152 is an inhibitory receptor of T cell activation, which is similar to the mammalian CD152. Overall, this study begins to define the interaction feature between primordial CD80/86 and its receptors CD28 and CD152 in teleost fish, alongside providing a cross-species understanding of the evolution of the costimulatory signals throughout vertebrates. |
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ISSN: | 1664-3224 1664-3224 |
DOI: | 10.3389/fimmu.2022.885005 |