Crystal structures of two I-Ad-peptide complexes reveal that high affinity can be achieved without large anchor residues.
We have determined the structures of I-Ad covalently linked to an ovalbumin peptide (OVA323-339) and to an influenza virus hemagglutinin peptide (HA126-138). The floor of the peptide-binding groove contains an unusual beta bulge, not seen in I-E and DR structures, that affects numerous interactions between the alpha and beta chains and bound peptide. Unlike other MHC-peptide complexes, the peptides do not insert any large anchor residues into the binding pockets of the shallow I-Ad binding groove. The previously identified six-residue "core" binding motif of I-Ad occupies only the P4 to P9 pockets, implying that specificity of T cell receptor recognition of I-Ad-peptide complexes can be accomplished by peptides that only partially fill the MHC groove.
Scott
C A
CA
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Peterson
P A
PA
Teyton
L
L
Wilson
I A
IA
D000818:Animals; D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry*; D000949:Histocompatibility Antigens Class II / Q000737:chemistry* / Q000235:genetics; D051379:Mice; D018448:Models, Immunological; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000737:chemistry*; D010446:Peptide Fragments / Q000737:chemistry*; D011994:Recombinant Proteins / Q000737:chemistry
C111391:HA 126-138; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D000949:Histocompatibility Antigens Class II; C111389:I-Ad antigen; C111390:OVA 323-339; D010446:Peptide Fragments; D011994:Recombinant Proteins; D010047:Ovalbumin