Peptide-MHC Interaction: A Rational Approach to Vaccine Design

The goal of vaccination is to induce a protective immune response without inducing the disease itself or other undesirable effects. In the past this was achieved by giving inactivated or attenuated pathogens, with notable success in some cases, but problems of safety, efficacy or production in others. A currently pursued alternative is the construction of synthetic peptide vaccines that contain pathogen-derived determinants able to induce an immune response both at the B and the T cell level. Because T cells recognize peptide fragments which are derived from the processing of soluble proteins [1], the technical problems of epitope conformation can be largely avoided in the design of synthetic T cell sites. However the constraints presented by the extensive polymorphism of MHC antigens on one hand [2], and the obligate interaction between the antigenic peptide and the MHC molecule on the other [3], create a problem for the immune system. When an antigenic determinant does not interact favorably with the MH...