T Cell Tolerance and Antigen Presenting Cell Function in the Thymus
The repertoire of T cell receptor specificities is shaped by two processes that occur in the thymus, positive and negative selection (1-5). Positive selection is responsible for generating a T cell repertoire that has the ability to recognize antigenic peptides in association with self-major histocompatibility complex (MHC) molecules. The other process is called negative selection, and assures that tolerance for self-antigens is achieved. During negative selection, potentially autoreactive T cells (i. e. those with high affinity for “self” antigens presented on self-MHC molecules) are actually deleted from the T cell repertoire (2, 6, 7) or are clonally inactivated (1, 8). “Self” is defined here as those self or foreign antigens which are present in the thymus at the moment of selection, a prime moment for which appears to be the early neonatal period: neonatally thymectomized mice develop a variety of tissue-specific autoimmune diseases later in life (9-11). Although factors controlling these autoimmune diseases are poorly understood, defects in clonal inactivation and clonal deletion may induce autoimmune diseases (9, 11, 12).
KeywordsNegative Selection Cell Tolerance Cell Repertoire Costimulatory Signal Clonal Deletion
Unable to display preview. Download preview PDF.
- 3.Zuniga-Pflucker JC, Jones LA, Chin LT, Kruisbeek AM (1991) CD4 and CD8 act as co-receptors during thymic selection of the T cell repertoire. Sem Immunol 3, 167–175.Google Scholar
- 12.Frontiers in Research: Immunological Tolerance. (1990) Science 248, 1335–1393.Google Scholar