Next Article in Journal
Dual Roles of the AMP-Activated Protein Kinase Pathway in Angiogenesis
Next Article in Special Issue
Genetic Association between Swine Leukocyte antigen Class II Haplotypes and Reproduction Traits in Microminipigs
Previous Article in Journal
Autoantibodies Specific to ERα are Involved in Tamoxifen Resistance in Hormone Receptor Positive Breast Cancer
Previous Article in Special Issue
Intramolecular Domain Movements of Free and Bound pMHC and TCR Proteins: A Molecular Dynamics Simulation Study
Open AccessArticle

HLA-DQA1 and HLA-DQB1 Alleles, Conferring Susceptibility to Celiac Disease and Type 1 Diabetes, Are More Expressed Than Non-Predisposing Alleles and Are Coordinately Regulated

Institute of Genetics and Biophysics “Adriano Buzzati Traverso”-CNR, 80131 Naples, Italy
Institute of Biochemistry and Cell Biology-CNR, 80131 Naples, Italy
Department of Translational Medical Science (DISMET), Section of Pediatrics, University of Naples Federico II, 80131 Naples, Italy
Author to whom correspondence should be addressed.
Co-first authors.
Co-last authors.
Cells 2019, 8(7), 751;
Received: 25 June 2019 / Revised: 9 July 2019 / Accepted: 16 July 2019 / Published: 19 July 2019
(This article belongs to the Special Issue Major Histocompatibility Complex (MHC) in Health and Disease)
HLA DQA1*05 and DQB1*02 alleles encoding the DQ2.5 molecule and HLA DQA1*03 and DQB1*03 alleles encoding DQ8 molecules are strongly associated with celiac disease (CD) and type 1 diabetes (T1D), two common autoimmune diseases (AD). We previously demonstrated that DQ2.5 genes showed a higher expression with respect to non-CD associated alleles in heterozygous DQ2.5 positive (HLA DR1/DR3) antigen presenting cells (APC) of CD patients. This differential expression affected the level of the encoded DQ2.5 molecules on the APC surface and established the strength of gluten-specific CD4+ T cells response. Here, we expanded the expression analysis of risk alleles in patients affected by T1D or by T1D and CD comorbidity. In agreement with previous findings, we found that DQ2.5 and DQ8 risk alleles are more expressed than non-associated alleles also in T1D patients and favor the self-antigen presentation. To investigate the mechanism causing the high expression of risk alleles, we focused on HLA DQA1*05 and DQB1*02 alleles and, by ectopic expression of a single mRNA, we modified the quantitative equilibrium among the two transcripts. After transfection of DR7/DR14 B-LCL with HLA-DQA1*05 cDNA, we observed an overexpression of the endogenous DQB1*02 allele. The DQ2.5 heterodimer synthesized was functional and able to present gluten antigens to cognate CD4+ T cells. Our results indicated that the high expression of alpha and beta transcripts, encoding for the DQ2.5 heterodimeric molecules, was strictly coordinated by a mechanism acting at a transcriptional level. These findings suggested that, in addition to the predisposing HLA-DQ genotype, also the expression of risk alleles contributed to the establishment of autoimmunity. View Full-Text
Keywords: autoimmunity; risk genes; expression; regulation autoimmunity; risk genes; expression; regulation
Show Figures

Figure 1

MDPI and ACS Style

Farina, F.; Picascia, S.; Pisapia, L.; Barba, P.; Vitale, S.; Franzese, A.; Mozzillo, E.; Gianfrani, C.; Del Pozzo G, G. HLA-DQA1 and HLA-DQB1 Alleles, Conferring Susceptibility to Celiac Disease and Type 1 Diabetes, Are More Expressed Than Non-Predisposing Alleles and Are Coordinately Regulated. Cells 2019, 8, 751.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

Back to TopTop