HBV epitopes, which are presented by HLA-A*0201 antigens, have already been identified. HLA-A*0201 antigen is most frequently seen among Caucasians. Groups from the Western countries have previously made analyses by using these epitopes. Among the Japanese, however, only 10% has HLA-A*0201, while as many as 70% have HLA-A*2402. It was, therefore, considered desirable to reveal HBV epitopes presented by HLA-A*2402, and investigate CTL recognition of HBV in Japanese patients with hepatitis B. We were able to identify two epitopes presented by HLA-A*2402 by using Reverse Immunogenetics. We then made a tetramer with these epitopes, and established a method to directly measure HBV-specific CD8 T cells in the peripheral blood from patients with acute and chronic hepatitis B.

Analysis of HBV-specific CD8 T cells in patients with acute hepatitis using tetramer and antibodies specific for CD28 and CD45RA demonstrated increasing number of CD8 T cells. The analysis of acute and chronic hepatitis C patients showed that the number of HBV-specific CD8 T cells in the peripheral blood is less in chronic hepatitis patients than in patients with acute hepatitis. Further, it made clear the increased relation between viral load and the number of specific CD8 T cells. These facts imply a possibility that CTLs control viral replication in patients with chronic hepatitis (J. Hepatology. 36: 105-115, 2002).