5IT2

Structure of a transglutaminase 2-specific autoantibody 693-10-B06 Fab fragment

Summary for 5IT2

• Entry DOI: 10.2210/pdb5it2/pdb
• Descriptor: heavy chain, light chain (3 entities in total)
• Functional Keywords: transglutaminase 2, autoantibody, fab fragment, immune system
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 47889.53

Authors

Chen, X.,Dalhus, B.,Hnida, K.,Iversen, R.,Sollid, L.M. (deposition date: 2016-03-16, release date: 2017-03-22, Last modification date: 2024-10-30)

Primary citation

Di Niro, R.,Mesin, L.,Zheng, N.Y.,Stamnaes, J.,Morrissey, M.,Lee, J.H.,Huang, M.,Iversen, R.,du Pre, M.F.,Qiao, S.W.,Lundin, K.E.,Wilson, P.C.,Sollid, L.M.
High abundance of plasma cells secreting transglutaminase 2-specific IgA autoantibodies with limited somatic hypermutation in celiac disease intestinal lesions
Nat. Med., 18:441-445, 2012

PubMed Abstract: Celiac disease is an immune-mediated disorder in which mucosal autoantibodies to the enzyme transglutaminase 2 (TG2) are generated in response to the exogenous antigen gluten in individuals who express human leukocyte antigen HLA-DQ2 or HLA-DQ8 (ref. 3). We assessed in a comprehensive and nonbiased manner the IgA anti-TG2 response by expression cloning of the antibody repertoire of ex vivo-isolated intestinal antibody-secreting cells (ASCs). We found that TG2-specific plasma cells are markedly expanded within the duodenal mucosa in individuals with active celiac disease. TG2-specific antibodies were of high affinity yet showed little adaptation by somatic mutations. Unlike infection-induced peripheral blood plasmablasts, the TG2-specific ASCs had not recently proliferated and were not short-lived ex vivo. Altogether, these observations demonstrate that there is a germline repertoire with high affinity for TG2 that may favor massive generation of autoreactive B cells. TG2-specific antibodies did not block enzymatic activity and served as substrates for TG2-mediated crosslinking when expressed as IgD or IgM but not as IgA1 or IgG1. This could result in preferential recruitment of plasma cells from naive IgD- and IgM-expressing B cells, thus possibly explaining why the antibody response to TG2 bears signs of a primary immune response despite the disease chronicity.

PubMed: 22366952
DOI: 10.1038/nm.2656

Experimental method

X-RAY DIFFRACTION (1.7 Å)