Abstract
We proposed a strategy (cassette theory) in which non-binding peptides for murine major histocompatibility complex (MHC) class II molecules are introduced into a MHC-binding component to render the resultant hybrid peptides bound to the MHC and thus immunogenic in animals carrying the relevant MHC. It was shown that 46F/HA127–133/54A(18mer) peptide which was prepared by introducing hemagglutinin (HA)127–133 of influenza virus into the H-2A b binding component induced significant T cell responses and antibodies (Ab) specific for HA127–133 in H-2A b mice. Further we found that the H-2A b binding component had a supermotif for human class II molecules (i.e. HLA-DQ6). In the present study, a new peptide vaccine, H3–H3, was prepared by combining 46F/HA127–133/54A(18mer) as a carrier and HA127–133 attached to the C terminus of 46F/HA127–133/54A(18mer) as a hapten and the effect of vaccine was examined in DQ6 mice which carry HLA-DQ6 alone as MHC class II molecules and thus may be regarded as a model of the DQ6 positive individuals. Since 46F/HA127–133/54A(18mer) induced merely Ab against HA127-133, it was assumed that H3-H3 induced mainly HA127–133 specific Ab in DQ6 mice without undesirable Ab production against the carrier. Indeed, H3-H3 elicited T cell responses and induced HA127–133 specific Ab in DQ6 mice. Furthermore, administration of H3–H3 inhibited growth of influenza virus until 9 weeks after the last immunization in DQ6 mice.
Published Version
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