Different modes of variation for each BG lineage suggest different functions.

John Chattaway,Susan M Lea,Joseph J E Caesar,R Andrei Ramirez-Valdez,Paul E Chappell,Jim Kaufman

doi:10.1098/rsob.160188

Abstract

Mammalian butyrophilins have various important functions, one for lipid binding but others as ligands for co-inhibition of αβ T cells or for stimulation of γδ T cells in the immune system. The chicken BG homologues are dimers, with extracellular immunoglobulin variable (V) domains joined by cysteines in the loop equivalent to complementarity-determining region 1 (CDR1). BG genes are found in three genomic locations: BG0 on chromosome 2, BG1 in the classical MHC (the BF-BL region) and many BG genes in the BG region just outside the MHC. Here, we show that BG0 is virtually monomorphic, suggesting housekeeping function(s) consonant with the ubiquitous tissue distribution. BG1 has allelic polymorphism but minimal sequence diversity, with the few polymorphic residues at the interface of the two V domains, suggesting that BG1 is recognized by receptors in a conserved fashion. Any phenotypic variation should be due to the intracellular region, with differential exon usage between alleles. BG genes in the BG region can generate diversity by exchange of sequence cassettes located in loops equivalent to CDR1 and CDR2, consonant with recognition of many ligands or antigens for immune defence. Unlike the mammalian butyrophilins, there are at least three modes by which BG genes evolve.

Highlights

Many members of the B7 gene superfamily are cell surface molecules involved in regulation of the immune response, but some have functions outside of the immune system [1]
Soon after the first mammalian B7 molecule was identified as important in immune co-stimulation, two other members were described with non-immune functions: myelin oligodendrocyte glycoprotein (MOG), which is found on the membranes sheathing neurons, and butyrophilin, which is involved in the structure of milk fat globules [2,3,4,5]
The other butyrophilin (Btn), the Btn-like, and the selection and upkeep of intraepithelial T cells (SKINT) genes were described with important functions in the immune system

Summary

Introduction

Many members of the B7 gene superfamily are cell surface molecules involved in regulation of the immune response, but some have functions outside of the immune system [1]. Soon after the first mammalian B7 molecule was identified as important in immune co-stimulation, two other members were described with non-immune functions: myelin oligodendrocyte glycoprotein (MOG), which is found on the membranes sheathing neurons, and butyrophilin ( called Btn1A1), which is involved in the structure of milk fat globules [2,3,4,5]. The other butyrophilin (Btn), the Btn-like, and the selection and upkeep of intraepithelial T cells (SKINT) genes were described with important functions in the immune system. The Btn and Btn-like genes function as stimulatory or inhibitory co-regulators of ab T cells, or as ligands for gd T cells (reviewed in [6,7,8,9]). Otherwise the most closely related are the BG genes ( referred to as B-G in the older literature), long suspected to have roles in the immune response (reviewed in [14])

Methods

Results

Conclusion