Differential Binding of Pyruvate Dehydrogenase Complex-E2 Epitopes by DRB108:01 and DRB111:01 Is Predicted by Their Structural Motifs and Correlates with Disease Risk

• Published in: The Journal of immunology (1950) Vol. 190; no. 9; pp. 4516 - 4524
• Main Authors: Chow, I-Ting, James, Eddie A, Gates, Theresa J, Tan, Venus, Moustakas, Antonis K, Papadopoulos, George K, Kwok, William W
• Format: Journal Article
• Language: English
• Published: United States 01.05.2013
• Subjects: Alleles; Antigens, Viral - immunology; Antigens, Viral - metabolism; Autoimmunity - immunology; Dihydrolipoyllysine-Residue Acetyltransferase - immunology; Dihydrolipoyllysine-Residue Acetyltransferase - metabolism; Epitope Mapping - methods; Epitopes, T-Lymphocyte - immunology; Epitopes, T-Lymphocyte - metabolism; HLA-DRB1 Chains - genetics; HLA-DRB1 Chains - immunology; HLA-DRB1 Chains - metabolism; Humans; Liver Cirrhosis, Biliary - immunology; Liver Cirrhosis, Biliary - metabolism; Protein Binding; Protein Structure, Tertiary; Self Tolerance - immunology; Structure-Activity Relationship; T-Lymphocytes - immunology; T-Lymphocytes - metabolism

DRB1*08:01 (DR0801) and DRB1*11:01 (DR1101) are highly homologous alleles that have opposing effects on susceptibility to primary biliary cirrhosis (PBC). DR0801 confers risk and shares a key feature with other HLA class II alleles that predispose to autoimmunity: a nonaspartic acid at beta57. DR110...