ABSTRACT
The immune system of higher vertebrates is composed of a large complement of cellular and molecular tools that, while respecting self-constituents, detects and eliminates invading microorganisms, and sets up an immunological memory that decreases severity of recurrent infections. A prominent role in orchestrating such protective responses is played by specific regulatory or effector T cells, which, upon recognition of antigenic determinants at the surface of target cells, may promote B cell differentiation and antibody production, or directly destroy virally-infected, stressed and malignant cells. Paradoxically, however, T cell activity may, under certain circumstances, lead to very deleterious pathological consequences associated, for example, with inflammation, allergy or autoimmunity. In particular, as indicated by cell transfer experiments, antibody treatments and genetic manipulations in appropriate animal models, T cells acting as helper cells for autoantibody production or as cytotoxic cells appear to be an absolute requirement for the expression of both organ-specific and systemic autoimmune diseases. For these reasons, a growing interest in autoimmune pathology focuses on the characterization of specific T cell clonotypes that accumulate in association with disease progression, particularly in regard to the molecular features of their antigen T cell receptors (TCR), the identity of the inciting antigenic epitopes and the development of inhibitory therapeutic approaches. This chapter will review recent reports on the TCR as they relate to structure, gene diversity, antigen recognition and repertoire selection, and will summarize studies attempting to correlate autoimmune disease with TCR genomic composition, polymorphism and expression.
