The cluster of BTN genes in the extended major histocompatibility complex

We sequenced the 170-kb cluster of BTN genes in the extended major histocom patibility complex region, 4 Mb telomeric of human leukocyte antigen class I genes, at 6p22.1. The cluster consists of seven genes belonging to the ex panding B7/butyrophilin-like group, a subset of the immunoglobulin gene sup erfamily, The main complex is composed of six genes, from two subfamilies, BTN2 and BTN3, arranged in pairs, This alternating pattern must have evolve d by duplications of an original block of two genes, one from each subfamil y. The sequences from the two subfamilies share similar to 50% amino acid i dentity, By analysis of repeat elements within each block, these duplicatio ns may be dated to approximately 100 million years ago, at about the time o f the branching of the Rodentia and Primate lineages, The single BTN1A1 (bu tyrophilin) gene was positioned similar to 25 kb centromeric to the cluster . Each gene covers similar to 12 kb and consists of seven (BTN2 subfamily) or nine (BTN3 subfamily) coding exons, The predicted leader sequence, immun oglobulin-like IgV (variable)/IgC (constant) ectodomains, and the predicted transmembrane domain are encoded on separate exons and are separated from a B30.2 domain by a variable number of very short exons, 21 and 27 nucleoti des in length. BTN transcripts were detected in all tissues examined, Alter native splicing, involving particularly the carboxyl-terminal B30.2 domain, was a notable feature. Most transcripts of BTN2 subfamily genes contained this domain, whereas BTN3 genes did not. Using immunofluorescence, we showe d surface expression of BTN-green fluorescent protein fusions in mammalian cell transfectants. (C) 2001 Academic Press.