Gluten acts in concert with the HLA-DQ2 or -DQ8 genes of predisposition, the mechanistically involved autoantigen tissue transglutaminase (TG2), and the activation of adaptive immune response (CD4+ T and B cells) leading to enterocyte damage and the development of villous atrophy, the histological hallmark of CD. The gene discussed is CD4; the disease is Cowden disease.