Structural diversity of human class II histocompatibility molecules induced by peptide ligands.
SDS-PAGE analyses of stable HLA-DR1 complexes indicate that the binding of T cell epitopes can lead to multiple conformational variants. Whereas short T epitopes (<14-mer) induce complexes with apparent MW ranging from 47 to 57 kDa, longer peptides form generally high mobility complexes (44-45 kDa). The generation of HLA-DR1 conformational variants appears dependent on core peptide residues fitting inside the groove but can additionally be attributed to the presence of N- and C-terminal flanking residues (PFRs) acting as a complementary mechanism. These PFRs can jointly affect major histocompatibility complex class II conformation and stability, supporting the existence of alternative contacts at a distance from the classical binding site.
Georges
B
B
Laboratoire dImmunopathologie Cellulaire des Maladies Infectieuses, CNRS UMR 8527, Lille, France. bertrand.georges@ibl.fr
Loing
E
E
Neveu
R
R
Melnyk
O
O
Gras-Masse
H
H
Auriault
C
C
D020816:Amino Acid Motifs / Q000276:immunology; D000595:Amino Acid Sequence; D001665:Binding Sites / Q000276:immunology; D002942:Circular Dichroism; D004591:Electrophoresis, Polyacrylamide Gel; D018984:Epitopes, T-Lymphocyte / Q000378:metabolism; D006684:HLA-DR Antigens / Q000737:chemistry* / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000276:immunology; D011487:Protein Conformation; D013816:Thermodynamics
D018984:Epitopes, T-Lymphocyte; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D000949:Histocompatibility Antigens Class II; D008024:Ligands; D046911:Macromolecular Substances; D010446:Peptide Fragments; D010455:Peptides