Isoforms of the nonclassical class i MHC antigen H2-Q5 are enriched in brain and encode Qdm peptide

Nora E. Renthal, Paula A. Guidry, Sharmila Shanmuganad, William Renthal, Iwona Stroynowski

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Although the human nonclassical class Ib major histocompatibility AR complex (Mhc) locus, HLA-G, is known to act as an immune suppressor in immune-privileged sites, little is currently known regarding participation of the rodent class Ib Mhc in similar pathways. Here, we investigated the expression properties of the mouse nonclassical Mhc H2-Q5 k gene, previously detected in tumors and tissues associated with pregnancy. We find that H2-Q5 k is alternatively spliced into multiple novel isoforms in a wide panel of C3H tissues. Unlike other known class I MHC, it is most highly transcribed in the brain, where the classical class Ia Mhc products are scarce. The truncated isoforms are selectively enriched in sites of immune privilege and are translated into cell surface proteins in neural crest-derived transfected cells. Furthermore, we present data supporting a model whereby Q5k isoforms serve an immune-protective role by donating their Qdm leader peptide to Qa-1, in a pathway homologous to the HLA-G leader fragment binding HLA-E and inhibiting CD94/NKG2A-positive cytotoxic cells. In addition, we report a previously unknown homolog of H2-Q5 k in the C57BL/6 mouse, which encodes Qdm, but is transcribed solely into noncanonical isoforms. Collectively, these studies demonstrate that H2-Q5 k, and its homologous class I-like H2 b gene may play tissue-specific roles in regulating immune surveillance.

Original languageEnglish (US)
Pages (from-to)57-64
Number of pages8
JournalImmunogenetics
Volume63
Issue number1
DOIs
StatePublished - Jan 2011

Fingerprint

H-2 Antigens
Major Histocompatibility Complex
Protein Isoforms
HLA-G Antigens
Peptides
Brain
Neural Crest
Protein Sorting Signals
Inbred C57BL Mouse
Genes
Rodentia
Membrane Proteins
Pregnancy
mouse Q5 antigen
Neoplasms

Keywords

  • Class Ib
  • H2-Q5
  • Immune privilege
  • Nonclassical MHC
  • Qa-1
  • Qdm

ASJC Scopus subject areas

  • Immunology
  • Genetics

Cite this

Isoforms of the nonclassical class i MHC antigen H2-Q5 are enriched in brain and encode Qdm peptide. / Renthal, Nora E.; Guidry, Paula A.; Shanmuganad, Sharmila; Renthal, William; Stroynowski, Iwona.

In: Immunogenetics, Vol. 63, No. 1, 01.2011, p. 57-64.

Research output: Contribution to journalArticle

Renthal, Nora E. ; Guidry, Paula A. ; Shanmuganad, Sharmila ; Renthal, William ; Stroynowski, Iwona. / Isoforms of the nonclassical class i MHC antigen H2-Q5 are enriched in brain and encode Qdm peptide. In: Immunogenetics. 2011 ; Vol. 63, No. 1. pp. 57-64.
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