Negatively charged residues interacting with the p4 pocket confer binding specificity to DRB1*0401.
OBJECTIVE
To identify critical residues involved in the binding of a selective peptide to DRB1*0401.


METHODS
The binding of peptides to native or site-directed mutant DR molecules was evaluated using enzyme-linked immunosorbent assay and flow cytometry.


RESULTS
Amino acid substitutions at DR and peptide residues, which were predicted to contribute to interactions within the DR p4 pocket, had the greatest effects on the specificity of binding.


CONCLUSIONS
Differences in the peptide-binding repertoires of DR molecules may contribute to associations with autoimmune diseases.
Woulfe
S L
SL
Searle/Monsanto Co., St. Louis, MO 63198, USA.
Bono
C P
CP
Zacheis
M L
ML
Kirschmann
D A
DA
Baudino
T A
TA
Swearingen
C
C
Karr
R W
RW
Schwartz
B D
BD
D000595:Amino Acid Sequence; D004563:Electrochemistry; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006680:HLA Antigens; D006684:HLA-DR Antigens / Q000235:genetics / Q000378:metabolism*; D059811:HLA-DRB1 Chains; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship
D006680:HLA Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553505:HLA-DRB1*04:01 antigen; D010455:Peptides