The Relationship between HLA Class I and Class II Antigens and the Outcome of HCV Infection and Treatment

Abstract

Hepatitis C is a liver disease that is caused by the Hepatitis C virus (HCV). In the majority of cases (about 85%), the infections become chronic and slowly damage the liver over many years (Wang & Eckels 1999). Over time, the liver damage can lead to cirrhosis (or scarring) of the liver, end-stage liver disease, or cancer. Symptoms of both acute and chronic infections are easily confused with less serious and shorter-term illnesses. In most cases, by the time the disease becomes apparent, liver damage can be considerable and even irreversible (Hoofnagle 1998). Currently, there are about 200 million people worldwide who are infected with HCV, and 4.9 million of those people are in the United States, making it much more common than HIV infections (Koff & Dienstag 2002). The major histocompatibilty complex (MHC) is a cluster of genes, which primarily encodes for cell surface proteins that are involved in the majority of vertebrate immune responses (reviewed in Gruen & Weissman 1997). MHC genes encode for transmembrane glycoproteins that play a crucial role in cell-to-cell signaling during immune recognition (reviewed in So 1995 and Apanius et al. 1998). MHC proteins aid T-cells in recognizing foreign antigens and in distinguishing self from non-self by serving as antigen receptors that bind peptide fragments for cell surface presentation to T-lymphocytes (Yamazaki, et al. 1999). MCH genes are the most polymorphic of all mammalian genes (Lechler 1995). The mammalian paradigm of MCH organization consists of the immunologically important class I and class II genes organized as two distinct, but genetically linked, gene clusters separated by a region of unrelated class III genes. The human major histocompatibility complex, known as the human leukocyte antigen (HLA) region, is one of the most extensively studied regions of the human genome. Since HLA genes have been shown to be both highly conserved and extremely polymorphic it is thought that variations in the immune response may influence the outcome of many diseases, particularly HCV (Lechler 1995).