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

Swanberg, Maria LU ; Lidman, O; Padyukov, L; Eriksson, P; Akesson, E; Jagodic, M; Lobell, A; Khademi, M; Borjesson, O and Lindgren, CM, et al. (2005) In Nature Genetics 37(5). p.486-494
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,... (More)
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. (Less)
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Contribution to journal
publication status
published
subject
in
Nature Genetics
volume
37
issue
5
pages
486 - 494
publisher
Nature Publishing Group
external identifiers
  • pmid:15821736
  • wos:000228862300017
  • scopus:20944445879
ISSN
1546-1718
DOI
10.1038/ng1544
language
English
LU publication?
yes
id
44664a82-4696-465e-893f-8cbc1f578464 (old id 243180)
date added to LUP
2007-08-20 09:52:29
date last changed
2017-11-12 04:00:09
@article{44664a82-4696-465e-893f-8cbc1f578464,
  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.},
  author       = {Swanberg, Maria and Lidman, O and Padyukov, L and Eriksson, P and Akesson, E and Jagodic, M and Lobell, A and Khademi, M and Borjesson, O and Lindgren, CM and Lundman, P and Brookes, AJ and Kere, J and Luthman, Holger and Alfredsson, L and Hillert, J and Klareskog, L and Hamsten, A and Piehl, F and Olsson, T},
  issn         = {1546-1718},
  language     = {eng},
  number       = {5},
  pages        = {486--494},
  publisher    = {Nature Publishing Group},
  series       = {Nature Genetics},
  title        = {MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction},
  url          = {http://dx.doi.org/10.1038/ng1544},
  volume       = {37},
  year         = {2005},
}