Abstract
The gastrointestinal tract is populated by a multitude of specialized immune cells endowed with receptors for classical (class Ia) and nonclassical (class Ib) MHC proteins. To identify class I products that engage these receptors and impact immunity/tolerance, we studied gut-transcribed class Ib loci and their polymorphism in inbred, outbred, and wild-derived mice. Intestinal tissues enriched in epithelial cells contained abundant transcripts of ubiquitously expressed and preferentially gut-restricted Q and T class I loci. The latter category included the "blastocyst Mhc" gene, H2-Bl, and its putative paralog, Tw5. Expression of H2-Bl was previously detected only at the maternal/fetal interface, where it was proposed to induce immune tolerance via interactions with CD94/NKG2A receptors. Analysis of coding region polymorphism performed here revealed two major alleles of H2-Bl with conserved residues at positions critical for class I protein folding and peptide binding. Both divergent alleles are maintained in outbred and wild mice under selection for fecundity and pathogen resistance. Surprisingly, we found that alternative splicing of H2-Bl mRNA in gut tissues is prevalent and allele-specific. It leads to strain-dependent expression of diverse repertoires of canonical and noncanonical transcripts that may give rise to distinct ligands for intestinal NK cell, T cell, and/or intraepithelial lymphocyte receptors.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alternative Splicing*
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Amino Acid Sequence
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Animals
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Blastocyst / immunology
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Cell Line, Tumor
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Cells, Cultured
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Gastric Mucosa / metabolism*
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H-2 Antigens / genetics*
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H-2 Antigens / metabolism
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HLA Antigens / genetics*
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HLA Antigens / metabolism
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HLA-G Antigens
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Histocompatibility Antigens Class I / genetics*
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Histocompatibility Antigens Class I / metabolism
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Humans
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Intestinal Mucosa / metabolism*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred C3H
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Mice, Inbred C57BL
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Mice, Inbred ICR
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Molecular Sequence Data
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Protein Isoforms / genetics
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Protein Isoforms / metabolism
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Protein Structure, Tertiary
Substances
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H-2 Antigens
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HLA Antigens
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HLA-G Antigens
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Histocompatibility Antigens Class I
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Protein Isoforms
Associated data
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GENBANK/AY989821
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