Naturally processed peptides from HLA-DQ7 (alpha1*0501-beta1*0301): influence of both alpha and beta chain polymorphism in the HLA-DQ peptide binding specificity.
Self peptides bound to HLA-DQ7 (alpha1*0501-beta1*0301), one of the HLA molecules associated with protection against insulin-dependent diabetes mellitus, were characterized after their acid elution from immunoaffinity-purified HLA-DQ7 (alpha1*0501-beta1*0301) molecules. The majority of these self peptides derived from membrane-associated proteins including HLA class I, class II, class II-associated invariant chain peptide and the transferrin-receptor (TfR). By in vitro binding assays, the specificity of these endogenous peptides for HLA-DQ7 (alpha1*0501-beta1*0301) molecules was confirmed. Among these peptides, the binding specificity of the TfR 215-230 self peptide was further examined on a variety of HLA-DQ and DR dimers. Several findings emerged from this analysis: (1) this peptide displayed HLA-DQ allelic specificity, binding only to HLA-DQ7 (alpha1*0501-beta1*0301); (2) when either the DQalpha or DQbeta chain was exchanged, little or no binding was observed, indicating that specificity of HLA-DQ peptide binding was determined by polymorphic residues of both the alpha and beta chains. (3) Unexpectedly, the TfR 215-230 self peptide, eluted from DQ, was promiscuous with regard to HLA-DR binding. This distinct DR and DQ binding pattern could reflect the structure of these two molecules as recently evidenced by crystallography.
Khalil-Daher
I
I
Laboratoire d'Immunogénétique Humaine, INSERM Unité 396, Institut Biomédical des Cordeliers and Hôpital Saint Louis, Paris, France.
Boisgérault
F
F
Feugeas
J P
JP
Tieng
V
V
Toubert
A
A
Charron
D
D
D000483:Alleles; D000595:Amino Acid Sequence; D006683:HLA-DQ Antigens / Q000235:genetics / Q000378:metabolism*; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism*; D011110:Polymorphism, Genetic; D011990:Receptors, Transferrin / Q000378:metabolism
D006683:HLA-DQ Antigens; C069546:HLA-DQ7 antigen; D006684:HLA-DR Antigens; D010446:Peptide Fragments; D011990:Receptors, Transferrin