Identification of a sequence that mediates promiscuous binding of invariant chain to MHC class II allotypes.
The invariant chain (Ii) shows promiscuous binding to a great variety of MHC class II allotypes. In contrast, the affinities of the Ii-derived fragments, class II-associated Ii peptides, show large differences in binding to class II allotypes. The promiscuous association of Ii to all class II polypeptides therefore requires an additional contact site to stabilize the interaction to the polymorphic class II cleft. We constructed recombinant molecules containing the class II binding site of Ii (CBS) and tested their association with HLA-DR dimers. The CBS fused to the transferrin receptor mediates binding of transferrin receptor-CBS to class II dimers. Within the CBS, deletion of a sequence N-terminal to the groove-binding motif abolished binding of Ii to DR. A promiscuous class II binding site was identified by reinsertion of the N-terminal residues, amino acids 81-87, of Ii into an Ii mutant that lacks the groove-binding segment. DR allotype-dependent association of Ii was achieved by insertion of antigenic sequences. The promiscuous association, in contrast to the class II allotype-dependent binding of Ii, is important to prevent interaction of class II dimers to nascent polypeptides in the endoplasmic reticulum.
Siebenkotten
I M
IM
Division of Immunobiology, University of Bonn, Germany.
Carstens
C
C
Koch
N
N
D000595:Amino Acid Sequence; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism*; D001665:Binding Sites / Q000235:genetics / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009980:Influenza A virus; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D011485:Protein Binding / Q000235:genetics / Q000276:immunology; D011990:Receptors, Transferrin / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000378:metabolism; D017384:Sequence Deletion / Q000276:immunology; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism
D000944:Antigens, Differentiation, B-Lymphocyte; D000949:Histocompatibility Antigens Class II; C031540:M-protein, influenza virus; D011990:Receptors, Transferrin; D011993:Recombinant Fusion Proteins; D014763:Viral Matrix Proteins; C045084:invariant chain