Plasmodium yoelii: Peptide immunization induces protective CD4⁺ T cells against a previously unrecognized cryptic epitope of the circumsporozoite protein

In this study we characterized the CD4⁺ T cell response directed against two distinct epitopes located in the circumsporozoite (CS) protein of Plasmodium yoelii. The immunization of mice with P. yoelii sporozoites induced CD4⁺ T cells which were mostly directed against one of these peptides, Py-1, previously reported to contain a CD4⁺ epitope. The CD4⁺ T cells directed against this immunodominant epitope were mostly of the Th-1 type. Another newly identified peptide, AS44, induced a specific CD4⁺ T cell response, which was mainly detectable after immunization with the corresponding peptide. Several CD4⁺ T cell clones, recognizing this epitope, were generated and their lymphokine expression was characterized, as well as their surface markers and their anti-parasite activity in vivo. It was noteworthy that some of these CD4⁺ T cell clones, which recognize this cryptic epitope and were of different Th subtypes, were shown to have a strong inhibitory effect on the development of liver stages of malaria parasites.