PREFERENTIAL RECOGNITION OF HEPATITIS-B NUCLEOCAPSID ANTIGENS BY TH-1 OR TH-2 CELLS IS EPITOPE AND MAJOR HISTOCOMPATIBILITY COMPLEX-DEPENDENT

Regulatory T-helper (Th) cells have been categorized into two functional subsets, Th-1 and Th-2 cells, which produce distinct lymphokines. In general, Th-1 cells mediate cellular immune responses and Th-2 cells mediate humoral immunity. Recent serological studies suggest that the Th-1-Th-2 balance may be relevant in acute and chronic hepatitis B virus (HBV) infections. The purpose of this study was to determine the potential of the nucleocapsid antigens (Ags) (hepatitis B core and e Ags [HBc/eAg]) of HBV to preferentially elicit either a Th-1 or a Th-2 dominant response. For this purpose, H-2 congenic B10.S and B10 mice were immunized with HBc/eAg, and Ag-specific T-cell proliferative responses, T-cell helper function, and T-cell cytokine production were analyzed. The results indicated that B10.S mice preferentially develop a Th-1-like response whereas B10 mice preferentially develop a Th-2-like response after immunization with HBc/eAg. Furthermore, the preferential Th-1 and Th-2 response patterns were reproduced when 12-residue peptides representing the dominant HBc/eAg-specific T-cell sites for B10.S (peptide 120-131) and B10 (peptide 129-140) mice were used as immunogens. Therefore, the combination of the T-cell site recognized and the major histocompatibility complex restricting element can in large part determine the Th phenotype of the HBc/eAg specific T-cell response. Other factors that influenced Th phenotype were the presence of exogenous cytokines, Ag structure, and tissue distribution.