CELLULAR RECOGNITION AND HLA RESTRICTION OF A MIDSEQUENCE HBSAG PEPTIDE IN HEPATITIS-B VACCINATED INDIVIDUALS

Vaccination with native HBsAg results in both a humoral and a cellular immune response in humans. In individuals who responded to vaccinatio n, the HBsAg (S region) specific response, as measured by cell prolife ration, diminished significantly after 12 weeks, a time when the antib ody response was still vigorous. Reduced and nonreduced HBsAg were equ ivalent in eliciting lymphocyte proliferation. Anti-MHC class II monoc lonal antibodies were used in blocking studies to demonstrate that ant i-HLA-DR but not anti-HLA-DQ or anti-HLA-DP inhibited specific lymphoc yte proliferation to HBsAg. Both the monomer (reduced) and dimer (nonr educed) forms of an immunodominant midsequence HBsAg peptide (amino ac id residues 139-146) produced lymphocyte proliferation roughly compara ble to that induced by whole HBsAg in 6 of 7 responders immunized with whole HBsAg and the peptide-induced proliferation was blocked by anti -HLA-DR but not by anti-HLA-DP antibodies. These results suggest that HBsAg p 139-146 is a major immunodominant peptide of HBsAg and is rest ricted by HLA-DR.