POSSIBLE ROLE OF PRES2 PEPTIDES PRESENTED BY MHC CLASS-I ANTIGEN IN THE PATHOGENESIS OF CHRONIC HEPATITIS-B

Many variations exist in the first 39 nucleotides of the preS2 (pre-S2 : 1-39) region of the HBV genome. Based on the similarities of their c oding amino acid sequences to those of prototype HBV, they were classi fied into 3 different types, adr-preS2, adw-preS2 and ayw-preS2. To cl arify the meaning of these variabilities in the preS2 region, we studi ed the HLA class I phenotype of chronic hepatitis B patients having hi gh levels of serum ALT. Our results indicated that in 12 of 14 chronic hepatitis patients infected with HBV type adr-preS2 had HLA-A24 pheno type whereas all of 7 patients infected with either adw- or ayw-preS2 HBV had HLA-A2 phenotype. This strong association between HLA class I phenotype and certain preS2 types of HBV infection was found only in p atients with high serum ALT levels but not in patients with almost nor mal levels of serum ALT. Our results therefore suggest that in the gen eration of chronic hepatitis B a suitable combination between a fragme nt of preS2 antigen and HLA class I antigens of the infected host, suc h as adr-preS2 with HLA-A24 and either adw- or ayw-preS2 with HLA-A2, might be required.