PMID: 2478618Nov 15, 1989Paper

Functional identification of agretopic and epitopic residues within an HBcAg T cell determinant.

The Journal of Immunology : Official Journal of the American Association of Immunologists
D R MilichJ E Jones

Abstract

Residues 120-131 within the hepatitis B core Ag (HBcAg) represent a dominant T cell recognition site for mice of the H-2S haplotype. This study was undertaken in order to identify residues within the p120-131 sequence which either interact with the TCR termed epitopic residues or interact with MHC class II molecules termed agretopic residues. For this purpose a panel of analogs of p120-131 composed of peptides containing single alanine substitutions for each residue was synthesized. These peptides were analyzed functionally for their ability to stimulate p120-131 or HBcAg-primed T cells and for their immunogenicity in B10.S or [B10.S X B10 (nonresponder)]F1 mice. Furthermore, analogs of p120-131 were used as stimulators and inhibitors of T cell activation in competitive inhibition experiments. Cumulatively these functional studies allowed us to identify residue 125 as a dominant epitopic residue and residues 127 and 129 as dominant agretopic residues. Furthermore, a p120-131 analog containing an alanine substitution for the dominant agretopic residue was immunogenic in B10.S mice, but was nonimmunogenic in (B10.S X B10)F1 mice indicating that T cell responsiveness is influenced by MHC class II gene dosage effects and can be inh...Continue Reading

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