Identification of a Nonameric H-2K sub K-Restricted CD8+ Cytotoxic T LymphocyteEpitope on the Plasmodium Falciparum Circumsporozoite Protein

摘要

A major focus of malaria vaccine development is the induction of CD8(+) cytotoxicT lymphocytes (CTL), which destroy infected hepatocytes (9, 10). This is because the sterile protective immunity induced by immunization of some strains of mice with radiation-attenuated sporozoites is eliminated by in vivo depletion of CD8+ T cells (27, 38) and because adoptive transfer of CD8(+) CTL against the Plasmodium berghi (26) and P. yoelii (24, 37) circumsporozoite proteins (PbCSP and PyCSP, respectively) and against the P. yoelii sporozoite surface protein 2 (13) completely protect against sporozoite challenge. The P. falciparum CSP (PfCSP) is a target for such malaria vaccine development. A 23-amino-acid peptide, PfCSP 7G8 368-390, has been demonstrated to include at least one CD8(+) CTL epitope in B10.BR mice (11, 14, 17, 34) and in humans (8, 16, 29), including one HLA-B35-restricted nonamer epitope (8). Peptides of 8 to 10 amino acids bind optimally to class I major histocompatibility complex (MHC) molecules for recognition of CD8+ CTL, and the development of optimal malaria vaccines may depend on the identification of such short peptides. The current studies were designed to identify for the first time a non amer peptide within PfCSP 368-390 that optimally sensitizes H-2k target cells for cytolysis by CD8+ CTL and to identify the H-2k molecule to which the peptide binds. pg1. JMD.