T-CELL REPERTOIRE AND AUTOIMMUNE-DISEASES

Self-reactivity and autoimmunity are processes related to the breakage of self-tolerance that can be distinguished by their different clinic al outcome and are widely accepted corner-stones of immunology. The fi nding that several potentially autoaggressive cells contribute to the repertoire of healthy individuals has stimulated a great deal of exper imental work aimed at understanding the mechanisms that prevent autoim mune pathology. In this review we will consider the basic principles, and our present knowledge of the rules that preside over the interplay of the immune system with self-components. One viewpoint stresses the importance of major histocompatibility complex (MHC) and non-MHC gene s in determining genetic predisposition to develop autoimmune phenomen a. At a different level there is a strong interest in understanding th e mechanisms of processing and presentation of self antigens, especial ly during ontogeny. Another topic of major interest concerns the inter action between MHC genes and the T cell receptor (TcR) complex as well as the identification of TcR V genes that are preferentially expresse d by autoimmune T cells. All of these aspects are evaluated in the con text of tolerance based on deletion and anergy. Finally we will propos e a general model of autoimmunity based on the most recent findings co ncerning the biological activity of exogenous superantigens.