Characterization of the anti-tissue transglutaminase antibody response in nonobese diabetic mice.
Type 1 diabetes mellitus is an autoimmune disorder characterized by destruction of insulin-producing pancreatic beta cells by T lymphocytes. In nonobese diabetic (NOD) mice, a role has been hypothesized for dietary gluten proteins in the onset of diabetes, and because gluten dependence is the major feature of celiac disease, together with production of Abs to the autoantigen tissue transglutaminase (tTG), we looked for the presence of anti-tTG Abs in the serum of NOD mice and, to establish their origin, analyzed the Ab repertoire of NOD mice using phage display Ab libraries. We found significant levels of serum anti-tTG Abs and were able to isolate single-chain Ab fragments to mouse tTG mainly from the Ab libraries made from intestinal lymphocytes and to a lesser extent from splenocytes. Data from NOD mice on a gluten-free diet suggest that the anti-tTG response is not gluten-dependent. The intestinal Ab response to tTG is a feature of NOD mice, but the underlying mechanisms remain obscure.
Sblattero
Daniele
D
Department of Biology, University of Trieste, Trieste, Italy. daniele@icgeb.org
Maurano
Francesco
F
Mazzarella
Giuseppe
G
Rossi
Mauro
M
Auricchio
Salvatore
S
Florian
Fiorella
F
Ziberna
Fabiana
F
Tommasini
Alberto
A
Not
Tarcisio
T
Ventura
Alessandro
A
Bradbury
Andrew
A
Marzari
Roberto
R
Troncone
Riccardo
R
D000595:Amino Acid Sequence; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis* / Q000097:blood; D001483:Base Sequence; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000276:immunology* / Q000378:metabolism; D018753:Diet, Protein-Restricted; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000276:immunology*; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005983:Glutens; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D007143:Immunoglobulin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D007147:Immunoglobulin Light Chains / Q000096:biosynthesis / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D019151:Peptide Library; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011994:Recombinant Proteins / Q000737:chemistry / Q000276:immunology; D027041:Somatic Hypermutation, Immunoglobulin; D011503:Transglutaminases / Q000235:genetics / Q000276:immunology*
D001323:Autoantibodies; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D019151:Peptide Library; D011994:Recombinant Proteins; D005983:Glutens; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins