Analysis of the permissive association of a malaria T cell epitope with DR molecules.
In this study we examined the association of a promiscuous malaria T cell epitope, CS.T3, to different HLA-DR alleles. A large series of singly substituted or truncated variants of CS.T3 was prepared and tested for the ability to be recognised in association with, or to bind to, three distinct HLA-DR alleles (DR1, DRw11, and DRw14(w6)) and three natural variants of HLA-DRw11. We found that although association with the different DR molecules mapped to identical or closely overlapping regions of the peptide, distinct substitutions could drastically influence the capacity of the peptide to interact with one but not another of the three DR molecules tested. Based on analysis of the distribution of residues recognized by T cell clones restricted to the different DR alleles, we suggest that the peptide CS.T3 is not bound, at least for the three DR examined, as an alpha-helix. In addition we tested three subtypes of DRw11 as APC for the CS.T3 analogues and observed that the peptide is most likely bound in the same conformation to the three natural variants of the DRw11 molecule.
Central Research Units, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
J
J
Kilgus
T
T
Jardetzky
J C
JC
Gorga
A
A
Trzeciak
D
D
Gillessen
F
F
Sinigaglia
D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000276:immunology*; D001665:Binding Sites; D002460:Cell Line; D000939:Epitopes; D006684:HLA-DR Antigens / Q000378:metabolism*; D059810:HLA-DR Serological Subtypes; D006801:Humans; D066298:In Vitro Techniques; D008288:Malaria / Q000276:immunology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology*; D011485:Protein Binding; D011487:Protein Conformation; D015800:Protozoan Proteins; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology*
D000953:Antigens, Protozoan; D000939:Epitopes; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; C080766:HLA-DR11 antigen; D010446:Peptide Fragments; D015800:Protozoan Proteins; D011948:Receptors, Antigen, T-Cell; C041595:circumsporozoite protein, Protozoan