Cell activation and immunogenicity

Abstract

There is presently great interest in the production of synthetic vaccines which utilize as immunogens peptides representing portions of protein antigens, either free or conjugated to protein carriers. The use of such immunogens raises questions regarding the cells which are activated an the characteristics of the resulting immune response. Using the tobacco mosaic virus protein (TMVP) as a model antigen, immune induction by the protein and by synthetic vaccines related to this protein was investigated. Specifically we have compared immune induction by the parent protein, an unconjugated eicosapeptide representing residues 93-112 of the protein, and an immunogen consisting of the C-terminal decapeptide of the above eicosapeptide conjugated to the protein carrier KLH. The comparison led to the following conclusions: Immunization with the free eicosapeptide but not with its C-terminal decapeptide leads to the activation of T and B lymphocytes. Immunization with the free eicosapeptide or with its C-terminal decapeptide-KLH conjugate induces antibodies capable of reacting with the parent protein. The isotype composition of the antibodies induced by these immunogens is similar to that induced by immunization with the whole protein. The fine specificity of the antibodies induced by all three immunogens is similar. However, the antibody populations induced by the synthetic immunogens may be devoid of one or more clonotypes depending upon constraints imposed by cellular interaction. Antigen specific T helper cells do not seem to influence the fine specificity of antibodies induced to a given epitope. Comparison of the induction of memory responses by the three immunogens led to the conclusion that immunization with the peptide hapten conjugated to the heterologous carrier KLH does not lead to an anamnestic antibody response upon encounter with the native protein. Immunization with an immunogenic peptide representing a portion of the protein recognized by T and B lymphocytes leads to an anamnestic antibody response upon encounter with the native protein.