Mass spectrometric identification of an HLA-A*0201 epitope from Plasmodium falciparum MSP-1.
Cytotoxic T lymphocytes (CTL) directed against Plasmodium falciparum-derived antigens were shown to play an important role for the protection against malaria. Although several CTL epitopes have been identified from P. falciparum sporozoite-derived antigens, none has been described for the merozoite form. Since the merozoite surface protein (MSP)-1 is a known target of the immune response, we focused on this protein to identify HLA-A*0201-associated epitopes. Using our mass spectrometry-based method [the 'predict-calibrate-detect' (PCD) approach], we were able to identify an MSP-1-derived epitope in the peptide mixture naturally associated with HLA-A*0201 molecules purified from an MSP-1-expressing cell line. CTLs against this epitope were generated from HLA-A*0201 monochain transgenic mice (HHD). They specifically killed MSP-1-expressing HLA-A2-positive target cells. Thus, we describe here the first MHC class I epitope from the merozoite form of P. falciparum. This epitope can be used as a tool for the immunomonitoring of natural or vaccine-induced CTL immune responses against malaria and could eventually be proposed as a component of an anti-malaria peptide-based vaccine.
Carralot
Jean-Philippe
JP
Department of Immunology, Institute for Cell Biology, University of Tübingen, Auf der Morgenstelle 15, D-72076 Tübingen, Germany.
Lemmel
Claudia
C
Stevanovic
Stefan
S
Pascolo
Steve
S
D000818:Animals; D000953:Antigens, Protozoan / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D018604:Epitope Mapping; D018984:Epitopes, T-Lymphocyte / Q000032:analysis* / Q000737:chemistry; D015789:HLA-A2 Antigen / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D016778:Malaria, Falciparum / Q000276:immunology; D013058:Mass Spectrometry; D020066:Merozoite Surface Protein 1 / Q000032:analysis* / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010963:Plasmodium falciparum / Q000737:chemistry / Q000276:immunology*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000378:metabolism
D000953:Antigens, Protozoan; D018984:Epitopes, T-Lymphocyte; D015789:HLA-A2 Antigen; D020066:Merozoite Surface Protein 1; D010455:Peptides