Antigen presentation and self-nonself discrimination.
Self-nonself discrimination is primarily carried out by T cells. Since the ligand recognized by T cells is a complex formed by antigenic peptides bound to MHC molecules, positive and negative selection of T lymphocytes must be based on the recognition of complexes formed by self-peptides bound to MHC molecules. This requires that self-antigens are continuously processed, bound by MHC molecules, and presented to T cells under conditions inducing both positive selection of T cells potentially able to recognize foreign antigens and negative selection, either by physical deletion or functional inactivation, of potentially autoreactive T cells. Self-nonself discrimination is not confined to intrathymic development of T lymphocytes, but it is a continuing process among peripheral T cells. Accordingly, autoimmunity is induced when self-antigens, or foreign antigens cross-reactive with self antigens, bound to MHC molecules, are presented under conditions able to activate self-reactive T cells. Based on these premises, a way of interfering with the induction of autoimmune diseases could rely on blocking the MHC binding site presenting the autoantigen.
Adorini
L
L
Preclinical Research, Sandoz Ltd., Basel, Switzerland.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology; D008958:Models, Molecular; D011485:Protein Binding / Q000276:immunology