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

Regulatory T-helper (Th) cells have been categorized into two function al subsets, Th-1 and Th-2 cells, which produce distinct lymphokines. I n 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 vi rus (HBV) infections. The purpose of this study was to determine the p otential of the nucleocapsid antigens (Ags) (hepatitis B core and e Ag s [HBc/eAg]) of HBV to preferentially elicit either a Th-1 or a Th-2 d ominant response. For this purpose, H-2 congenic B10.S and B10 mice we re immunized with HBc/eAg, and Ag-specific T-cell proliferative respon ses, T-cell helper function, and T-cell cytokine production were analy zed. The results indicated that B10.S mice preferentially develop a Th -1-like response whereas B10 mice preferentially develop a Th-2-like r esponse after immunization with HBc/eAg. Furthermore, the preferential Th-1 and Th-2 response patterns were reproduced when 12-residue pepti des representing the dominant HBc/eAg-specific T-cell sites for B10.S (peptide 120-131) and B10 (peptide 129-140) mice were used as immunoge ns. Therefore, the combination of the T-cell site recognized and the m ajor histocompatibility complex restricting element can in large part determine the Th phenotype of the HBc/eAg specific T-cell response. Ot her factors that influenced Th phenotype were the presence of exogenou s cytokines, Ag structure, and tissue distribution.