Identification of Caucasian CD4 T cell epitopes on the circumsporozoite protein of Plasmodium vivax. T cell memory.

Abstract

We have identified a population of Caucasians with a defined past history of infection with Plasmodium vivax malaria. Using purified synthetic peptides overlapping the sequence of the circumsporozoite protein, we determined the percentage of individuals whose T cells proliferated or secreted IFN-gamma in response to peptide stimulation, for both this population and a population of nonmalaria-exposed control individuals. A number of peptides were recognized by both groups, but 11 peptides were uniquely recognized by the exposed population, and thus represented malaria-specific T cell epitopes. CD4 T cells were found to be responsible for the proliferative response. Humans last exposed to vivax sporozoites as long ago as 49 yr responded as well or better to these malaria-specific epitopes as individuals exposed within the previous month. Since such malaria-induced memory response may not be a feature of Plasmodium falciparum infections, and since P. falciparum does not have a persisting hypnozoite stage, our data argue that the persistence of T cell memory to vivax epitopes may result from antigenic persistence in the liver.

Prolonged antigen presentation is required for optimal CD8+ T cell responses against malaria liver stage parasites (137.16)

“…This may have important implications for immune responses in endemic areas where people are exposed to sporozoites on a daily to monthly basis; if antigen is retained similarly in humans it would mean many people would be permanently exposed to sporozoite antigen [41]. There is some evidence that antigen persistence has a positive role in these circumstances -T cell responses to P. vivax which forms long lived hypnozoite stages in the liver are generally more robust and long lived than responses to P. falciparum, at least among travelers and individuals in areas of low transmission [42,43]. However, paradoxically, given our results showing that antigen persistence has a positive role in the development of immune responses, T cell responses to sporozoite antigens are generally considered rather poor in individuals in endemic areas [44].…”