TG2-gluten complexes as antigens for gluten-specific and transglutaminase-2 specific B cells in celiac disease.

A hallmark of celiac disease is the gluten-dependent production of antibodies specific for deamidated gluten peptides (DGP) and the enzyme transglutaminase 2 (TG2). Both types of antibodies are believed to result from B cells receiving help from gluten-specific CD4+ T cells and differentiating into antibody-producing plasma cells. We have here studied the collaboration between DGP- and TG2-specific B cells with gluten-specific CD4+ T cells using transgenic mice expressing celiac patient-derived T-cell and B-cell receptors, as well as between B-cell transfectants and patient-derived gluten-specific T-cell clones.

A high-affinity human TCR-like antibody detects celiac disease gluten peptide-MHC complexes and inhibits T cell activation.

Antibodies specific for peptides bound to human leukocyte antigen (HLA) molecules are valuable tools for studies of antigen presentation and may have therapeutic potential. Here, we generated human T cell receptor (TCR)-like antibodies toward the immunodominant signature gluten epitope DQ2.5-glia-α2 in celiac disease (CeD).

Generation of an HLA-DQ2.5 Knock-In Mouse.

The human MHC class II molecule HLA-DQ2.5 is implicated in multiple autoimmune disorders, including celiac disease, type 1 diabetes, and systemic lupus erythematosus. The pathogenic contribution of HLA-DQ2.

B cell tolerance and antibody production to the celiac disease autoantigen transglutaminase 2.

Autoantibodies to transglutaminase 2 (TG2) are hallmarks of celiac disease. To address B cell tolerance and autoantibody formation to TG2, we generated immunoglobulin knock-in (Ig KI) mice that express a prototypical celiac patient-derived anti-TG2 B cell receptor equally reactive to human and mouse TG2. We studied B cell development in the presence/absence of autoantigen by crossing the Ig KI mice to Tgm2-/- mice.

Robust DNA repair in PAXX-deficient mammalian cells.

To ensure genome stability, mammalian cells employ several DNA repair pathways. Nonhomologous DNA end joining (NHEJ) is the DNA repair process that fixes double-strand breaks throughout the cell cycle. NHEJ is involved in the development of B and T lymphocytes through its function in V(D)J recombination and class switch recombination (CSR).

Normal development of mice lacking PAXX, the paralogue of XRCC4 and XLF.

DNA repair consists of several cellular pathways which recognize and repair damaged DNA. The classical nonhomologous DNA end-joining (NHEJ) pathway repairs double-strand breaks in DNA. It is required for maturation of both B and T lymphocytes by supporting V(D)J recombination as well as B-cell differentiation during class switch recombination (CSR).