Identification of T cell epitopes on the 33-kDa fragment of Plasmodium yoelii merozoite surface protein 1 and their antibody-independent protective role in immunity to blood stage malaria.
Merozoite surface protein 1 (MSP1) of malaria parasites undergoes proteolytic processing at least twice before invasion into a new RBC. The 42-kDa fragment, a product of primary processing, is cleaved by proteolytic enzymes giving rise to MSP1(33), which is shed from the merozoite surface, and MSP1(19), which is the only fragment carried into a new RBC. In this study, we have identified T cell epitopes on MSP1(33) of Plasmodium yoelii and have examined their function in immunity to blood stage malaria. Peptides 20 aa in length, spanning the length of MSP1(33) and overlapping each other by 10 aa, were analyzed for their ability to induce T cell proliferation in immunized BALB/c and C57BL/6 mice. Multiple epitopes were recognized by these two strains of mice. Effector functions of the dominant epitopes were then investigated. Peptides Cm15 and Cm21 were of particular interest as they were able to induce effector T cells capable of delaying growth of lethal P. yoelii YM following adoptive transfer into immunodeficient mice without inducing detectable Ab responses. Homologs of these epitopes could be candidates for inclusion in a subunit vaccine.
Wipasa
Jiraprapa
J
Cooperative Research Center for Vaccine Technology, Queensland Institute of Medical Research, Royal Brisbane Hospital, Queensland, Australia.
Hirunpetcharat
Chakrit
C
Mahakunkijcharoen
Yuvadee
Y
Xu
Huji
H
Elliott
Salenna
S
Good
Michael F
MF
D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000502:physiology*; D002460:Cell Line / Q000637:transplantation; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000032:analysis* / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D007113:Immunity, Innate; D016056:Immunodominant Epitopes / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D008288:Malaria / Q000097:blood / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D020066:Merozoite Surface Protein 1 / Q000008:administration & dosage / Q000032:analysis / Q000276:immunology / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D016513:Mice, SCID; D008969:Molecular Sequence Data; D008970:Molecular Weight; D010446:Peptide Fragments / Q000008:administration & dosage / Q000032:analysis / Q000276:immunology / Q000627:therapeutic use; D010967:Plasmodium yoelii / Q000254:growth & development* / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000637:transplantation
D000913:Antibodies, Protozoan; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D010446:Peptide Fragments