The butyrophilin (BTN) gene family: from milk fat to the regulation of the immune response
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REVIEW
The butyrophilin (BTN) gene family: from milk fat to the regulation of the immune response Hassnae Afrache & Philippe Gouret & Shanaiz Ainouche & Pierre Pontarotti & Daniel Olive
Received: 27 January 2012 / Accepted: 19 April 2012 # Springer-Verlag 2012
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 Electronic supplementary material The online version of this article (doi:10.1007/s00251-012-0619-z) contains supplementary material, which is available to authorized users. H. Afrache : P. Gouret : S. Ainouche : P. Pontarotti (*) : D. Olive (*) Aix Marseille Université, Marseille, France e-mail: [email protected] e-mail: [email protected] P. Pontarotti e-mail: [email protected] H. Afrache : S. Ainouche : D. Olive INSERM, Unité 1068, CRCM, Marseille, France H. Afrache : S. Ainouche : D. Olive IPC, Marseille, France H. Afrache : P. Gouret : S. Ainouche : P. Pontarotti CNRS, LATP—EBM, UMR 7353, Marseille, France
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. Keywords Butyrophilins . Mammals . Phylogeny . Nomenclature . Immune system . Co-signaling
Introduction Butyrophilins (BTN) are type 1 membrane proteins belonging to the immunoglobulin (Ig) superfamily. They are characterized by the presence of extracellular Ig-like domains (IgV and/or IgC) with, for some family members, a cytoplasmic B30.2 domain. The extracellular BTN domains are structurally similar to those of the B7 family, a family of cosignaling molecules essential for the regulation of T cell activation and tolerance. The B7/CD28 family includes ligands and receptors involved both in T cell costimulation such as B7.1 (CD80), B7.2 (CD86), and their receptors (at least CD28), and in T cell co-inhibition such as PD-L1 (CD274), PD-L2 (CD-273), and their receptor (at least PD-1/CD279) (Greenwald et al. 2005). Linsley et al. (1994) have shown that the IgV domain of B7 molecules shares a sequence similarity with the IgV domain of two BTN: BTN1 and MOG. A phylogenetic study conducted by Compte e
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