The immune system victorious: selective preservation of self.

How the body successfully distinguishes its own tissue cells from those that are foreign and genetically nonidentical to it has been a focus of much research. Clonal deletion maintains that immune system cells with the potential to injure self constituents are eliminated during development, thereby neutralizing their capacity to induce self injury. Selected self-reactive maturing T cell clones undergo deletion in the thymus. A two-step selection process affects immature T cells that enter the thymus. Positive selection makes certain that all surviving cells are able to identify major histocompatibility complex (MHC) proteins present on all body cells. These MHC proteins interact with antigens and present them to T lymphocytes. Negative selection is essential for self-tolerance. It eliminates potentially injurious self-reactive T cells by placing them in contact with a mixture of self antigens in the thymus. Clonal anergy might act together with clonal deletion to maintain self tolerance. Self-reactive T cells in the blood of healthy subjects could represent cells whose affinities for antigen are too weak to initiate an immunologic disease. The fate of T cells reacting to a specific antigen has been traced in transgenic mice. Class I MHC molecules present peptides manufactured within the cell, whereas class II MHC molecules present peptides from extracellular proteins. Interaction of a T cell receptor with its homologous antigen associated with MHC molecules leads to proliferation of that T cell in the presence of costimulatory signals. Investigations elucidating the role of T cell receptors, MHC molecules and antigen peptides in self-nonself discrimination are discussed. The article concludes with an introductory summary of the remaining articles in the issue that address selected topics in self-nonself discrimination.