Degeneracy in T-cell antigen recognition - implications for the pathogenesis of autoimmune diseases.

T-cells recognize by their T-cell receptor (TCR) short peptides presented by major histocompatibility complex (MHC) molecules. Based on functional and structural data, it has become widely accepted that this interaction is highly flexible thus allowing a specific TCR to interact with a broad range of different peptide ligands. Although cross-reactivity is essential for selection and maintenance of the T-cell repertoire, it also carries the danger of inducing autoreactivity following protective immune responses. This hypothesis has been supported by a large number of findings in vitro and in vivo experimental systems. Here we discuss recent findings on cross-recognition of T-cells and provide a new experimental approach to address specificity and cross-reactivity in autoimmune disorders.