Are extensive T cell epitope polymorphisms in the Plasmodium falciparum circumsporozoite antigen, a leading sporozoite vaccine candidate, selected by immune pressure?

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.

A survey of the Th2R and Th3R allelic variants in the circumsporozoite protein gene of P. falciparum parasites from western Thailand.

Allelic variation in the Plasmodium falciparum circumsporozoite protein (CS) gene has been determined by sequencing the immunodominant T-cell epitopes, Th2R and Th3R, from 95 isolates from two malaria-endemic areas in the west of Thailand. Comparison with a reference sequence revealed only non-synonymous point mutations in the two epitope regions. Point mutations were found outside these epitopes in a minority of samples, and all but four were also non-synonymous.