In situ distribution of major histocompatibility complex products and viral antigens in chronic hepatitis B virus infection: evidence that HBc-containing hepatocytes may express HLA-DR antigens

Abstract

Using a double-staining immunohistochemical procedure, the topographical relationship between viral antigens on the one hand and the expression of major histocompatibility complex products by hepatocytes on the other hand was analyzed in a series of 19 liver biopsies from patients with chronic hepatitis B virus infection. In areas of piecemeal necrosis, periportal hepatocytes demonstrated Class I major histocompatibility complex products or HLA-A, B and C antigens, but did not show a preferential expression of either HBcAg or HBsAg. The cellular infiltrate of piecemeal necrosis consisted of helper/inducer and suppressor/cytotoxic T-lymphocytes, and was admixed in four cases with branching dendritic processes of sinusoidal lining cells which strongly expressed Class II major histocompatibility complex products or HLA-DR antigens. The latter surrounded small groups of periportal hepatocytes. In areas of spotty necrosis, the hepatocytes expressed HLA-A, B and C antigens in all cases, and were admixed with variable numbers of suppressor/cytotoxic T-lymphocytes. In 14 cases, the clustered hepatocytes in areas of spotty necrosis expressed HLA-DR antigens, associated in 11 of the cases with immunoreactive HBcAg in the nuclei of some of the HLA-DR-positive hepatocytes. Immunoelectron microscopy, performed in one such case, demonstrated the presence of HLA-DR antigen in a discontinuous pattern at the plasma membrane of some hepatocytes, together with the presence of core particles in the nucleus of HLA-DR-positive hepatocytes. Our findings further contribute to the growing evidence that HBcAg represents the major target antigen for T-cell attack in areas of spotty necrosis.(ABSTRACT TRUNCATED AT 250 WORDS)