Immune Pressure? Sporozoite Vaccine Candidate, Selected by Circumsporozoite Antigen, a Leading Plasmodium falciparum in the Are Extensive T Cell Epitope Polymorphisms

Protective cellular immune responses depend on MHC presentation of pathogen-derived Ag fragments. MHC diversity renders this process sensitive to point mutations coding for altered amino acid sequence of the short target Ag-derived peptides epitopes. Thus, in a given host, a pathogen with an altered epitope sequence will be more likely to escape detection and elimination by the immune system. At a population level, selection by immune pressure will increase the likelihood of polymorphism in important pathogen antigenic epitopes. This mechanism of immune evasion is found in viruses and other pathogens. The detection of polymorphic hot spots in an Ag is often taken as a strong indication of its role in protective immunity. We provide evidence that polymorphisms in the T cell epitopes of a malaria vaccine candidate are unlikely to have been selected by immune pressure in the human host. The Journal of Immunology, 2005, 175: 3935–3939. originating from Ratchaburi and Kanchanburi, as described above. The polymorphic regions present in three unlinked single-copy P. falciparum genes were as follows: block 2 of the merozoite surface protein 1 ( msp1 ), block 3 of the merozoite surface protein 2 ( msp2 and the RII region of the glutamate rich protein ( glurp ) were amplified according to a previously published nested PCR protocol (11). The products were electrophoresed 3% DNA was visualized an UV transil- luminator ethidium bromide Fragment of highest genetic