Immune Recognition of Stress Proteins in Infection and in Surveillance of Stressed Cells

Molecular biologists and immunologists have been investigating intensively the major antigens involved in the immune response to infection by mycobacteria, the causative agents of tuberculosis and leprosy. These two infectious diseases are a continuous threat to mankind. Recent WHO data indicates that as much as one third of the total population in the world is infected with Mycobacterium tuberculosis, and about 2–3 million people die from tuberculosis each year. About 10 million people in the world are infected with Mycobacterium leprae and stand at risk of incurring irreparable nerve damage (Bloom, 1989). The cloning and sequencing of genes coding for major mycobacterial protein antigens revealed that most of these proteins are members of stress protein (or heat shock protein) families (Young et al., 1988). This observation was unexpected because stress proteins occur in highly conserved forms in all organisms, from bacteria to man (Lindquist and Craig, 1988). The discovery raised questions about how immune cells could distinguish bacterial stress proteins and human stress proteins, and why the immune system would treat stress proteins as major targets when such recognition runs the risk of producing autoimmune disease (reviewed in Kaufmann, 1990; Young, 1990; Young and Elliott, 1989).