The mechanisms of self and non-self discrimination by T cells remain a fascinating topic for immunologists. How the immune system achieves protection of the host against an ever-changing realm of pathogens using a rather limited repertoire of T-cell receptors and at the same time avoids inflicting damage against its own tissues is equally puzzling. Although a better understanding of these questions has come from studies of the extent of cross reactivity of T-cell clones specific for foreign or self antigens, and also from examination of the different antigen avidities by which they recognize either type of antigen, many details are still lacking. Recently, there has been investigation into how T cells of the adaptive immune system can recognize functional protein domains or amino acid patterns. This type of T-cell reactivity is reminiscent of the pattern recognition that is firmly established as an important function of innate immune receptors such as Toll-like receptors. Many functional protein domains are conserved in evolution and are shared by a wide spectrum of pathogens, as well as by proteins of animals and humans. Hence, pattern recognition by adaptive immune cells might represent an efficient mechanism for host protection by the above-mentioned limited number of T-cell receptors. However, the fact that such functional domains occur so frequently in nature also implies that pattern recognition by T cells might cause autoimmunity, and recent data support this hypothesis.