Les autoanticorps antithyroperoxydase : de la construction de banques combinatoires de fragments d'anticorps à la localisation de la région immunodominante de la thyroperoxydase

Autoimmune thyroid diseases (AITD) are associated with a high production of anti-thyroperoxidase (TPO) autoantibodies (aAbs). Anti-TPO aAbs are invaluable markers for AITD diagnosis, furthermore they might play a role in the processes leading to thyroid destruction. To more easily study those aAbs, several recombinant human anti-TPO aAbs were isolated from phage antibody combinatorial libraries. Genetically, even though a restriction in their heavy (VH) and light (VL) chain variable regions gene usage has been shown, no correlation was found between VH/VL gene associations and epitopic recognition. Epitopically, it has been shown that a discontinuous but restricted domain on human TPO, named immunodominant region (IDR), contains most of the anti-TPO B-cell epitopes. Several groups highlighted that the IDR is composed of two overlapping domains named A and B. While the IDR/A-specific aAbs strongly interact with one major region (amino acid residues 599-617), the IDR/B-specific aAb epitopes are spread out on the molecule.