title: HLA-DR3 molecules can bind peptides carrying two alternative specific submotifs.
abstract: 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.
authors.affiliation: Department of Immunohematology, University Hospital, Leiden, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Geluk
authors.forename: K E
authors.initials: KE
authors.lastname: van Meijgaarden
authors.forename: S
authors.initials: S
authors.lastname: Southwood
authors.forename: C
authors.initials: C
authors.lastname: Oseroff
authors.forename: J W
authors.initials: JW
authors.lastname: Drijfhout
authors.forename: R R
authors.initials: RR
authors.lastname: de Vries
authors.forename: T H
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: A
authors.initials: A
authors.lastname: Sette
mesh_terms: 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
chemical_list: D000485:Allergens; D001426:Bacterial Proteins; D015803:HLA-DR3 Antigen; D009211:Myoglobin; D010455:Peptides