Roles of B7 homologue 3 protein (B7-H3) in T cell responses of large yellow croaker (Larimichthys crocea)

Abstract

The B7 family provides critical co-stimulatory signals for T cell activation through receptor interactions, thereby modulating T cell proliferation and function. However, the roles and downstream signaling pathways of these molecules in teleosts remain largely unexplored. In the present study, we identified a B7-H3 homologue (LcB7-H3) in large yellow croaker (Larimichthys crocea), a commercially significant marine teleost species. The deduced LcB7-H3 protein contains conserved extracellular IgV-like and IgC-like domains, and phylogenetic analysis revealed its clustering with vertebrate B7-H3 homologues. It is constitutively expressed in all examined tissues and immune cells, with particularly high expression levels in mucosal tissues and primary head kidney monocytes/macrophages (PKMs). The recombinant LcB7-H3 protein (rLcB7-H3) significantly enhanced T cell proliferation and upregulated interleukin-2 expression, which is a hallmark of teleost T cell activation. Furthermore, rLcB7-H3 increased phosphorylation levels of MEK1/2 and ERK1/2 in the MAPK/ERK signaling pathway, as well as mTOR and 4E-BP1 in the mTOR signaling pathway. Collectively, these findings demonstrate that LcB7-H3 may promote T cell proliferation and activation via MAPK/ERK and mTOR pathways, suggesting evolutionarily conserved roles among vertebrate B7-H3 homologues.