title: MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction.
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-gamma. 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.
authors.affiliation: Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Swanberg
authors.forename: Olle
authors.initials: O
authors.lastname: Lidman
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov
authors.forename: Per
authors.initials: P
authors.lastname: Eriksson
authors.forename: Eva
authors.initials: E
authors.lastname: Akesson
authors.forename: Maja
authors.initials: M
authors.lastname: Jagodic
authors.forename: Anna
authors.initials: A
authors.lastname: Lobell
authors.forename: Mohsen
authors.initials: M
authors.lastname: Khademi
authors.forename: Ola
authors.initials: O
authors.lastname: Börjesson
authors.forename: Cecilia M
authors.initials: CM
authors.lastname: Lindgren
authors.forename: Pia
authors.initials: P
authors.lastname: Lundman
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Brookes
authors.forename: Juha
authors.initials: J
authors.lastname: Kere
authors.forename: Holger
authors.initials: H
authors.lastname: Luthman
authors.forename: Lars
authors.initials: L
authors.lastname: Alfredsson
authors.forename: Jan
authors.initials: J
authors.lastname: Hillert
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.forename: Fredrik
authors.initials: F
authors.lastname: Piehl
authors.forename: Tomas
authors.initials: T
authors.lastname: Olsson
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D008285:Major Histocompatibility Complex; D009103:Multiple Sclerosis / Q000235:genetics*; D009203:Myocardial Infarction / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D013116:Spinal Cord / Q000276:immunology; D015534:Trans-Activators / Q000235:genetics*
chemical_list: D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators