Autoimmune Disease and T-cell Immunologic Recognition

The immune system has evolved T-cell receptors (TCRs) and B-cell receptors with exquisite specificity to distinguish self from nonself. On occasion, the immune system will attack self-components leading to autoimmune disease (for review, see Kumar et al. 1989). Approximately 4 years ago, we initiated studies of autoimmune responses based on several general concepts. First, it is clear that an understanding of the molecular features of immune recognition will be a key to understanding autoimmune responses since helper T (TH) cells are pivotal in initiating most immune responses. Specifically, we focused our efforts on the trimolecular complex responsible for TH-cell activation: (1) the TCR for antigen, (2) the antigen-presenting class II molecules encoded by the major histocompatibility complex (MHC), and (3) the peptide antigen (Fig. 1). Second, it is likely that the primary response to self-antigens may be limited, both with regard to the number of peptide epitopes employed for TH-cell...