The murine family of gut-restricted class Ib MHC includes alternatively spliced isoforms of the proposed HLA-G homolog, "blastocyst MHC".
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.
Guidry
Paula A
PA
Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9093, USA.
Stroynowski
Iwona
I
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001755:Blastocyst / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D005753:Gastric Mucosa / Q000378:metabolism*; D006183:H-2 Antigens / Q000235:genetics* / Q000378:metabolism; D006680:HLA Antigens / Q000235:genetics* / Q000378:metabolism; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary
D006183:H-2 Antigens; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I; D020033:Protein Isoforms