Perturbations in the T cell receptor ß repertoire during malaria infection in children: a preliminary study.

The changes occurring in the T cell repertoire during clinical malaria infection in children remain unknown. In this study, we undertook the first detailed comparative study of the T cell repertoire in African children with and without clinical malaria to test the hypothesis that clonotypic expansions that occur during P. falciparum infection will contribute to the generation of a T cell repertoire that is unique to each disease state. We profiled the complementarity-determining region 3 (CDR3) of the TCRß chain sequences from children with Plasmodium falciparum infections (asymptomatic, uncomplicated and severe malaria) and compared these with sequences from healthy children. Strikingly, we discovered that children with symptomatic malaria has a lower TCR diversity and frequency of shared (or “public”) TCR sequences compared to asymptomatic children. Also, TCR diversity was inversely associated with parasitemia. Furthermore, by clustering TCR sequences based on their predicted antigen specificities, we identified a specificity cluster, with a 4-mer amino acid motif, that is overrepresented in the asymptomatic group compared to the diseased groups. Further investigations into this finding may help in delineating important antigenic targets for vaccine and therapeutic development. The results show that the T cell repertoire in children is altered during malaria, suggesting that exposure to P. falciparum antigens disrupts the adaptive immune response, which is an underlying feature of the disease. Overall design: Cross-sectional study to characterize T cell phenotypic responses in children with P. falciparum infections