The butyrophilin (BTN) gene family: from milk fat to the regulation of the immune response

Abstract

Butyrophilins (BTN) belong to the immunoglobulin (Ig) superfamily of transmembrane proteins. These molecules are of increasing interest to immunologists, as they share a structural homology with B7 family members at the extracellular domain level. Moreover, a role of these molecules has been suggested in the negative regulation of lymphocyte activation for almost all the BTN that have been studied. In addition, the expression of some BTN family members has been reported to be associated with autoimmune diseases. Over the last few years, the number of BTN and BTN-like members has greatly increased. In this study, the butyrophilin family in mammals has been revisited, using phylogenetic analysis to identify all the family members and the phylogenetic relations among them, and to establish a standard nomenclature. Fourteen BTN groups were identified that are not all conserved between mammalian species. In addition, an overview of expression profiles and functional BTN data demonstrates that these molecules represent a new area of investigation for the design of future strategies in the modulation of the immune system.

The Proto-MHC of Placozoans, a Region Specialized in Cellular Stress and Ubiquitination/Proteasome Pathways

“…In the absence of IFN, an antiviral activity of the T. adhaerens TRIM might proceed via direct binding (and ubiquitination) of viral proteins as for TRIM5 in primates, or via modulation of expression of other antiviral factors. Although TRIM genes and B30.2 domains are conservatively associated with vertebrate MHCs (and paralogons) (7,63), it is striking that they are also present in the MHC/neurotrophin regions in the ancestor of placozoans and bilaterians. More generally, our data show a preferential location of B30.2 proteins within T. adhaerens proto-MHC and proto-neurotrophin, supporting an ancestral and strongly conservative association of this domain associated with viral sensing or defense with the MHC-neurotrophin region as suggested previously (63).…”

“…To target counterparts of the MHC-related regions, we selected T. adhaerens scaffolds with highest density of best blast hits-that is, scaffolds in which the proportion of hits of at least one human gene was higher than a given threshold. A density threshold was set from the distribution at 23% to optimize the contrast between the groups, selecting the scaffolds 1, 2, 3,6,7,9,10,12,14,15,22,28,31,34,35,40, and 42 for further analysis. Protein sequences corresponding to the 6721 genes located within these scaffolds were extracted using Ensembl Biomart and blasted back against the human proteome using D-BLAST with an e-value cutoff of 1e-10.…”

Regulation of Immunity by Butyrophilins

“…Human immunoglobulin (Ig) superfamily receptor proteins of the butyrophilin and butyrophilin-like families, termed BTN and BTNL, have also been recognized as potentially important immune modulators (5)(6)(7)(8). The Ig domains from butyrophilins exhibit some structural features of the B7 family of coreceptors, such as CD80 and CD86, ICOS-L, and PD-L1 (9)(10)(11).…”

Adoptively transferred Vγ9Vδ2 T cells show potent antitumor effects in a preclinical B cell lymphomagenesis model

“…However, a challenge to modeling the actions of human Vδ2 + T cells in vivo is that rodents do not possess a similar isoprenoid-reactive γδ T cell subset, and lack the BTN3A1 isoform (25,26). Prior studies have thus xenografted established human tumors into immune-deficient mice in the presence or absence of human Vδ2 + T cells to evaluate their effects in vivo (27)(28)(29)(30)(31)(32).…”