title: The cluster of BTN genes in the extended major histocompatibility complex.
abstract: We sequenced the 170-kb cluster of BTN genes in the extended major histocompatibility complex region, 4 Mb telomeric of human leukocyte antigen class I genes, at 6p22.1. The cluster consists of seven genes belonging to the expanding B7/butyrophilin-like group, a subset of the immunoglobulin gene superfamily. The main complex is composed of six genes, from two subfamilies, BTN2 and BTN3, arranged in pairs. This alternating pattern must have evolved by duplications of an original block of two genes, one from each subfamily. The sequences from the two subfamilies share approximately 50% amino acid identity. By analysis of repeat elements within each block, these duplications may be dated to approximately 100 million years ago, at about the time of the branching of the Rodentia and Primate lineages. The single BTN1A1 (butyrophilin) gene was positioned approximately 25 kb centromeric to the cluster. Each gene covers approximately 12 kb and consists of seven (BTN2 subfamily) or nine (BTN3 subfamily) coding exons. The predicted leader sequence, immunoglobulin-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 nucleotides in length. BTN transcripts were detected in all tissues examined. Alternative 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 showed surface expression of BTN-green fluorescent protein fusions in mammalian cell transfectants.
authors.affiliation: Department of Immunology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, United Kingdom. dar32@mole.bio.cam.ac.uk
authors.forename: D A
authors.initials: DA
authors.lastname: Rhodes
authors.forename: M
authors.initials: M
authors.lastname: Stammers
authors.forename: G
authors.initials: G
authors.lastname: Malcherek
authors.forename: S
authors.initials: S
authors.lastname: Beck
authors.forename: J
authors.initials: J
authors.lastname: Trowsdale
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D000071797:Butyrophilins; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D006224:Cricetinae; D018076:DNA, Complementary / Q000378:metabolism; D005091:Exons; D020224:Expressed Sequence Tags; D005819:Genetic Markers; D049452:Green Fluorescent Proteins; D006239:Haplotypes; D006367:HeLa Cells; D006720:Homozygote; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D008285:Major Histocompatibility Complex; D008562:Membrane Glycoproteins / Q000235:genetics*; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D008969:Molecular Sequence Data; D005810:Multigene Family; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D020038:RNA, Spliced Leader; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D014162:Transfection
chemical_list: C000605698:BTN1A1 protein, human; D000071797:Butyrophilins; D018076:DNA, Complementary; D005819:Genetic Markers; D008164:Luminescent Proteins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D020038:RNA, Spliced Leader; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins