The murine family of gut-restricted class Ib MHC includes alternatively spliced isoforms of the proposed HLA-G homolog, "blastocyst MHC"

Paula A. Guidry, Iwona Stroynowski

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The gastrointestinal tract is populated by a multitude of specialized immune cells endowed with receptors for classical (class Ia) and neoclassical (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.

Original languageEnglish (US)
Pages (from-to)5248-5259
Number of pages12
JournalJournal of Immunology
Volume175
Issue number8
StatePublished - Oct 15 2005

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HLA-G Antigens
Blastocyst
Protein Isoforms
Alleles
NK Cell Lectin-Like Receptor Subfamily C
Immune Tolerance
Protein Folding
Alternative Splicing
Natural Killer Cells
Fertility
Gastrointestinal Tract
Immunity
Epithelial Cells
Mothers
Lymphocytes
Ligands
T-Lymphocytes
Messenger RNA
Peptides
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

The murine family of gut-restricted class Ib MHC includes alternatively spliced isoforms of the proposed HLA-G homolog, "blastocyst MHC". / Guidry, Paula A.; Stroynowski, Iwona.

In: Journal of Immunology, Vol. 175, No. 8, 15.10.2005, p. 5248-5259.

Research output: Contribution to journalArticle

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