Since the discovery of human leukocyte antigen (HLA) as a genetic system, the search for the biological function of HLA molecules has been a very intense and attractive area of immunological research. It has been a major factor in the development of our understanding of the role of T cells in the initiation and regulation of autoimmune diseases. The currently increasing incidences of chronic inflammatory diseases, such as allergies but also several autoimmune diseases, possibly due to our Westernized modern life-style, are asking for novel intervention or prevention strategies. Heat shock proteins (or stress proteins) can be an example of relevant microbial antigens with an intrinsic capacity to trigger anti-inflammatory T cell regulation. Heat shock proteins may be part of an ancient system, which includes several stress-induced self-antigens, seen by a self-protective immune system. Peptide-based intervention, including clinical trials with HSP60 and HSP70 peptides, is now an area of intensive clinical research.