Genomics, isoforms, expression, and phylogeny of the MHC class I-related MR1 gene.
A growing number of non-MHC-encoded class I-related molecules have been shown to perform diverse, yet essential, functions. These include T cell presentation of bacterially derived glycolipidic Ags by CD1, transcytosis of maternal IgG by the neonatal Fc receptor, enriched presence and plausible function within exocrine fluids of the Zn-alpha2-glycoprotein, subversion of NK cytolytic activity by the CMV UL18 gene product, and, finally, crucial involvement in iron homeostasis of the HFE gene. A recently described member of this family is the MHC class-I related (MR1) gene. The most notable feature of MR1 is undoubtedly its relatively high degree of sequence similarity to the MHC-encoded classical class I genes. The human chromosome 1q25.3 MR1 locus gives rise not only to the originally reported 1,263-bp cDNA clone encoding a putative 341-amino acid polypeptide chain, but to many additional transcripts in various tissues as well. Here we define the molecular identity of all human and murine MR1 isoforms generated through a complex scenario of alternative splicing, some encoding secretory variants lacking the Ig-like alpha3 domain. Moreover, we show ubiquitous transcription of these MR1 variants in several major cell lineages. We additionally report the complete 18,769-bp genomic structure of the MR1 locus, localize the murine orthologue to a syntenic segment of chromosome 1, and provide evidence for conservation of a single-copy MR1 gene throughout mammalian evolution. The 90% sequence identity between the human and mouse MR1 putative ligand binding domains together with the ubiquitous expression of this gene favor broad immunobiologic relevance.
Basel Institute for Immunology, Switzerland.
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Riegert
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Wanner
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Bahram
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D005805:Genes, MHC Class I; D015894:Genome, Human; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D051379:Mice; D015778:Minor Histocompatibility Antigens; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D015395:Histocompatibility Antigens Class I; C094840:MR1 protein, human; D015778:Minor Histocompatibility Antigens; C490628:Mr1 protein, mouse; D020033:Protein Isoforms