HLA-DR3 molecules can bind peptides carrying two alternative specific submotifs.
Three different HLA-DR3-specific peptide binding motifs have been proposed. These motifs shared a major hydrophobic anchor at the N-terminus, but differed in the C-terminal anchor residues. In the present study, the structural requirements for peptide binding to HLA-DR3 were examined in further detail by using quantitative HLA-DR3-specific binding assays and sets of single substitution analogues of DR3 binding peptides (Lol pollen amino acids 171-190 and sperm whale myoglobin amino acids 132-151). We found that the requirements for binding to HLA-DR3 vary among different DR3 binding peptides; the absence of an anchor or the presence of only a weak anchor residue at either position n or n + 3 can be compensated for by the presence of a strong, positively charged anchor residue at position n + 5. These results explain several of the previously reported differences between DR3-specific peptide binding motifs. To evaluate the predictive value of the thus-refined motif, the DR3 binding capacity of an overlapping set of peptides, spanning the entire sequence of the 65-kDa heat shock protein of Mycobacterium tuberculosis was investigated and correlated with the occurrence of the different DR3 motifs. A strong correlation was found between the presence of the refined DR3 motif and peptide binding to purified HLA-DR3 molecules.
Geluk
A
A
Department of Immunohematology, University Hospital, Leiden, The Netherlands.
van Meijgaarden
K E
KE
Southwood
S
S
Oseroff
C
C
Drijfhout
J W
JW
de Vries
R R
RR
Ottenhoff
T H
TH
Sette
A
A
D000485:Allergens / Q000235:genetics / Q000276:immunology; D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001665:Binding Sites; D015803:HLA-DR3 Antigen / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D008129:Lolium / Q000235:genetics / Q000276:immunology; D008969:Molecular Sequence Data; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000276:immunology; D009211:Myoglobin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011058:Pollen / Q000235:genetics / Q000276:immunology; D011485:Protein Binding
D000485:Allergens; D001426:Bacterial Proteins; D015803:HLA-DR3 Antigen; D009211:Myoglobin; D010455:Peptides