Features of T-cell recognition and antigen structure useful in the design of vaccines to elicit T-cell immunity.

In contrast to antibodies, T lymphocytes tend to recognize a limited number of immunodominant antigenic sites on a protein antigen. Therefore, the effective design of synthetic or recombinant fragment vaccines would be better approached if these sites could be identified. From studies of the processing and genetically restricted presentation of the model protein antigen myoglobin to murine T cells, certain general principles have emerged which should be useful in this endeavour. The immunodominant sites for helper T cells in model proteins tend to be regions which can fold as alpha-helices and, in particular, helices which are amphipathic, i.e. which have a hydrophobic side and a hydrophilic side separated in space. These two sides may serve to interact with the major histocompatibility molecule on the antigen-presenting cell and with the T-cell receptor, respectively. A computer algorithm has been developed to search for such sites in protein sequences and it has been applied to two proteins of interest for vaccine development, the circumsporozoite protein of Plasmodium falciparum malaria and the envelope protein of the AIDS virus (HIV). Corresponding peptides were synthesized and shown to induce helper and/or proliferative T-cell immunity.