Promiscuous and allele-specific anchors in HLA-DR-binding peptides.
The major histocompatibility complex (MHC) class II molecules are highly polymorphic membrane glycoproteins that bind peptide fragments of proteins and display them for recognition by CD4+ T cells. To understand the effect of human MHC class II polymorphism on peptide-MHC interaction, we have isolated M13 phage from a large M13 peptide display library by selection with DRB1*0401 and DRB1*1101 molecules, as recently described for DRB1*0101. Sequence analysis of the peptide-encoding region of DR-bound phage led to the identification of position-specific anchor residues, defining motifs for peptide binding to DR molecules. The three DR motifs share two anchor residues at relative positions 1 and 4, while allele-specific anchor residues have been identified at position 6. These results provide a biophysical basis for both the promiscuity and the specificity of peptide recognition by DR molecules.
Hammer
J
J
Roche Milano Ricerche, Italy.
Valsasnini
P
P
Tolba
K
K
Bolin
D
D
Higelin
J
J
Takacs
B
B
Sinigaglia
F
F
D000483:Alleles; D000595:Amino Acid Sequence; D017104:Bacteriophage M13 / Q000378:metabolism*; D001665:Binding Sites; D006684:HLA-DR Antigens / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D016415:Sequence Alignment
D006684:HLA-DR Antigens; D010455:Peptides