MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction

Research output: Contribution to journalArticle

Abstract

Antigen presentation to T cells by MHC molecules is essential for adaptive immune responses. To determine the exact position of a gene affecting expression of MHC molecules, we finely mapped a previously defined rat quantitative trait locus regulating MHC class II on microglia in an advanced intercross line. We identified a small interval including the gene MHC class II transactivator (Mhc2ta) and, using a map over six inbred strains combined with gene sequencing and expression analysis, two conserved Mhc2ta haplotypes segregating with MHC class II levels. In humans, a - 168A --> G polymorphism in the type III promoter of the MHC class II transactivator (MHC2TA) was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction, as well as lower expression of MHC2TA after stimulation of leukocytes with interferon-γ. We conclude that polymorphisms in Mhc2ta and MHC2TA result in differential MHC molecule expression and are associated with susceptibility to common complex diseases with inflammatory components.

Details

Authors
  • Maria Swanberg
  • O Lidman
  • L Padyukov
  • P Eriksson
  • E Akesson
  • M Jagodic
  • A Lobell
  • M Khademi
  • O Borjesson
  • CM Lindgren
  • P Lundman
  • AJ Brookes
  • J Kere
  • Holger Luthman
  • L Alfredsson
  • J Hillert
  • L Klareskog
  • A Hamsten
  • F Piehl
  • T Olsson
Organisations
External organisations
  • Karolinska Institutet
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
Original languageEnglish
Pages (from-to)486-494
JournalNature Genetics
Volume37
Issue number5
Publication statusPublished - 2005
Publication categoryResearch
Peer-reviewedYes