Regulation of porcine classical and nonclassical MHC class I expression

Tennant, Laura M, Renard, Christine, Chardon, Patrick and Powell, Penny P ORCID: (2007) Regulation of porcine classical and nonclassical MHC class I expression. Immunogenetics, 59 (5). pp. 377-89. ISSN 0093-7711

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Major histocompatibility complex (MHC) class I molecules comprise a family of polymorphic cell surface receptors consisting of classical 1 a molecules that present antigenic peptides and nonclassical 1 b molecules. Gene expression for human classical and nonclassical MHC class I molecules has been shown to be differentially regulated by interferon, with variation in the nucleotide sequence of promoter regions, resulting in differences in interferon inducibility and basal levels of gene transcription. In this study on porcine classical and nonclassical swine leukocyte Ag (SLA) class I molecules, we show alignments of putative regulatory elements in the promoters of the three functional classical class I genes, SLA-1, SLA-2, and SLA-3; two nonclassical 1 b genes, SLA-6 and SLA-7; and a MIC-2 gene. Promoter elements were cloned upstream from a luciferase reporter gene, and the basal and inducible activities of each were characterized by expression in Max cells, an immortalized pig cell line that responds to interferon and tumor necrosis factor alpha (TNF-alpha). All three classical class I but not nonclassical promoters responded to interferon. This was confirmed by the transactivation of SLA-1, but not SLA-7, after the co expression with interferon regulatory factors (IRFs), IRF-1, IRF-2, IRF-3, IRF-7, and IRF-9. Classical class I genes were activated by cotransfection with nuclear factor kappa B (NF-kappaB) p65 and by treatment of cells with TNF-alpha, although, unlike human promoter there was no synergistic effect with interferon. The greatest effect on classical class I promoters was coexpression with the class II transactivator (CIITA), important for constitutive transactivation. These results determine the differential regulation of porcine classical and nonclassical MHC class I and reflects their importance in antigen presentation during infection.

Item Type: Article
Uncontrolled Keywords: animals,base sequence,cell membrane,cells, cultured,gene expression regulation,histocompatibility antigens class i,histocompatibility antigens class ii,molecular sequence data,nuclear proteins,promoter regions, genetic,sus scrofa,tata box,trans-activators
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Gastroenterology and Gut Biology
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
Depositing User: Pure Connector
Date Deposited: 12 Nov 2014 16:50
Last Modified: 19 Oct 2023 01:23
DOI: 10.1007/s00251-007-0206-x

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