title: HLA-DQ2.5 genes associated with celiac disease risk are preferentially expressed with respect to non-predisposing HLA genes: Implication for anti-gluten T cell response.
abstract: HLA genes represent the main risk factor in autoimmune disorders. In celiac disease (CD), the great majority of patients carry the HLA DQA1*05 and DQB1*02 alleles, both of which encode the DQ2.5 molecule. The formation of complexes between DQ2.5 and gluten peptides on antigen-presenting cells (APCs) is necessary to activate pathogenic CD4(+) T lymphocytes. It is widely accepted that the DQ2.5 genes establish the different intensities of anti-gluten immunity, depending whether they are in a homozygous or a heterozygous configuration. Here, we demonstrated that HLA DQA1*05 and DQB1*02 gene expression is much higher than expression of non-CD-associated genes. This influences the protein levels and causes a comparable cell surface exposure of DQ2.5 heterodimers between DQ2.5 homozygous and heterozygous celiac patients. As a consequence, the magnitude of the anti-gluten CD4(+) T cell response is strictly dependent on the antigen dose and not on the DQ2.5 gene configuration of APCs. Furthermore, our findings support the concept that the expression of DQ2.5 genes is an important risk factor in celiac disease. The preferential expression of DQ2.5 alleles provides a new functional explanation of why these genes are so frequently associated with celiac disease and with other autoimmune disorders.
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati Traverso" - CNR, Via Pietro Castellino, 111, 80131, Naples, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Pisapia
authors.affiliation: Institute of Food Sciences-CNR, Via Roma 52, 83100, Avellino, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Camarca
authors.affiliation: Institute of Protein Biochemistry-CNR, Via Pietro Castellino, 111, 80131, Naples, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Picascia
authors.affiliation: Institute of Food Sciences-CNR, Via Roma 52, 83100, Avellino, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Bassi
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati Traverso" - CNR, Via Pietro Castellino, 111, 80131, Naples, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Barba
authors.affiliation: Institute of Genetics and Biophysics "Adriano Buzzati Traverso" - CNR, Via Pietro Castellino, 111, 80131, Naples, Italy. Electronic address: giovanna.delpozzo@igb.cnr.it.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Del Pozzo
authors.affiliation: Institute of Protein Biochemistry-CNR, Via Pietro Castellino, 111, 80131, Naples, Italy. Electronic address: c.gianfrani@ibp.cnr.it.
authors.forename: Carmen
authors.initials: C
authors.lastname: Gianfrani
mesh_terms: D000483:Alleles; D017951:Antigen Presentation / Q000276:immunology; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D002446:Celiac Disease / Q000235:genetics* / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005983:Glutens / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics* / Q000276:immunology*; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology; D006801:Humans; D009980:Influenza A virus / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012306:Risk; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D018984:Epitopes, T-Lymphocyte; D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; D006684:HLA-DR Antigens; D012333:RNA, Messenger; D005983:Glutens
keywords: Antigen presentation; Celiac disease; Gene expression; HLA; T cell response