Stress proteins, autoimmunity, and autoimmune disease

Area of Science:

• Immunology
• Autoimmunity
• Molecular Biology

Background:

• The immune system initially recognizes microbial antigens for protection.
• Autologous stress proteins, like heat shock protein 60 (hsp60), are key in early host defense.
• Natural antibodies and T cells with gamma delta receptors play roles in recognizing these proteins.

Purpose of the Study:

• To explore the role of stress proteins in the development of autoimmune diseases.
• To investigate the mechanisms by which stress proteins may trigger self-nonself discrimination failure.
• To examine the involvement of stress proteins in conditions like rheumatoid arthritis and SLE.

Main Methods:

• Analysis of T cell responses to stress protein epitopes presented by class lb molecules.
• Investigation of molecular mimicry between bacterial stress proteins and host self-antigens.
• Identification of autoantibodies against stress proteins in patients with autoimmune diseases.

Main Results:

• Autoreactivity in arthritis initially involves gamma delta T cells recognizing hsp60 epitopes.
• Molecular mimicry, such as by a DnaJ stress protein epitope, may contribute to rheumatoid arthritis susceptibility.
• Autoantibodies to stress proteins are found in SLE and rheumatoid arthritis, though their pathogenic role is under investigation.

Conclusions:

• Stress proteins play a likely central role in the etiology of arthritis.
• Understanding stress protein involvement opens new avenues for investigating autoimmune diseases.
• Stress proteins may be key components in the "immunogenic particle" theory of autoantibody formation.