The Molecular Mechanisms of HLA Associated Autoimmunity

Abstract

The immune system of normal individuals represents a dynamic and highly regulated interplay between various types of effector cells programmed to respond to and eliminate invading pathogens, while maintaining a state of tolerance to self molecules. In contrast, an autoimmune disorder reflects a breakdown in the regulatory mechanisms that normally govern a humoral and cellular response so that self molecules are recognized as foreign, thereby triggering an autoimmune attack. For the majority of autoimmune disorders described to date, such as insulin-dependent diabetes mellitus (IDDM), rheumatoid arthritis (RA), and multiple sclerosis (MS), the nature of the specific immunoregulatory defect(s) causing the disease is largely unknown. Moreover, the critical factors that predispose an individual to a particular autoimmune disease remain unclear. However, some insight has been gained from numerous genetic studies over the last two decades describing a rather striking association between autoimmunity and molecules encoded within the HLA complex, namely the HLA class I and II antigens.

R. T. is a recipient of a Medical Research Council of Canada fellowship. L. F. is a recipient of an Alfred Benzon of Denmark fellowship. S. M. S. is a recipient of a predoctoral fellowship from the Howard Hughes Medical Institute.