MHC allele-specific binding of a malaria peptide makes it become promiscuous on fitting a glycine residue into pocket 6.
Peptide 1585 (EVLYLKPLAGVYRSLKKQLE) has a highly conserved amino-acid sequence located in the Plasmodium falciparum main merozoite surface protein (MSP-1) C-terminal region, required for merozoite entry into human erythrocytes and therefore represents a vaccine candidate for P. falciparum malaria. Original sequence-specific binding to five HLA DRB1* alleles (0101, 0102, 0401, 0701, and 1101) revealed this peptide's specific HLA DRB1*0102 allele binding. This peptide's allele-specific binding to HLA DRB1*0102 took on broader specificity for the DRB1*0101, -0401, and -1101 alleles when lysine was replaced by glycine in position 17 (peptide 5198: EVLYLKPLAGVYRSLKG(17)QLE). Binding of the identified G(10)VYRSLKGQLE(20) C-terminal register to these alleles suggests that peptide promiscuous binding relied on fitting Y(12), L(15), and G(17) into P-1, P-4, and P-6, respectively. The implications of the findings and the future of this synthetic vaccine candidate are discussed.
Vargas
Luis Eduardo
LE
Fundación Instituto de Inmunologi;a de Colombia (FIDIC), Carrera 50 No. 26-00. Bogotá, Colombia.
Parra
Carlos Alberto
CA
Salazar
Luz Mary
LM
Guzmán
Fanny
F
Pinto
Martha
M
Patarroyo
Manuel E
ME
D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D005998:Glycine / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D059811:HLA-DRB1 Chains; D006801:Humans; D008285:Major Histocompatibility Complex / Q000235:genetics* / Q000502:physiology; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1 / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding
D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D010455:Peptides; D005998:Glycine