Human T cell recognition of polymorphic epitopes from malaria circumsporozoite protein

Lymphocytes obtained from forty individuals living in a malaria endemic area of West Africa were tested for in vitro proliferative responses to peptides representing variant regions of the immunodominant T cell domain of the circumsporozoite protein (amino acids 326 to 345, referred to as Th2R, and 361 to 380, referred to as Th3R) from three distinct strains of Plasmodium falciparum. A total of 83% of the individuals responded to at least one of the six peptides tested, confirming that these epitopes are immunodominant. A much greater number of individuals than expected by chance (32% of the responders to Th2R and 27% of the responders to Th3R) reacted to all three of the variant peptides for that epitope, indicating interdependency of the T cell responses, suggestive of cross-reactivity. Nevertheless, some subjects' T cells were clearly able to distinguish each variant peptide from the others. Using EBV transformed B cells, lymphocytes from 10 of the individuals were HLA typed. In this small group, HLA DRw13 was associated with a positive response to any of the peptides, whereas there was a negative association between DQw3 and response to any of the peptides. These results, although limited by the small sample size, suggest that recognition of T epitopes may be Ir gene linked. Our findings suggest that it may be possible to broaden the immunogenicity of an anti-sporozoite malaria vaccine.