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.