NATURALLY PROCESSED PEPTIDES FROM HLA-DQ7 (ALPHA-1-ASTERISK-0501-BETA-1-ASTERISK-0301) - INFLUENCE OF BOTH ALPHA-CHAIN AND BETA-CHAIN POLYMORPHISM IN THE HLA-DQ PEPTIDE BINDING-SPECIFICITY

Self peptides bound to HLA-DQ7 (alpha 10501-beta 1*0301), one of the HLA molecules associated with protection against insulin-dependent dia betes mellitus, were characterized after their acid elution from immun oaffinity-purified HLA-DQ7 (alpha 10501-beta 1*0301) molecules. The m ajority of these self peptides derived from membrane-associated protei ns including HLA class I, Glass II, class Ii-associated invariant chai n peptide and the transferrin-receptor (TfR). By in vitro binding assa ys, the specificity of these endogenous peptides for HLA-DQ7 (alpha 1 0501-beta 10301) molecules was confirmed. Among these peptides, the b inding specificity of the TfR 215-230 self peptide was further examine d 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 (alpha 10501-beta 1*0301); (2) when either th e DQ alpha or DQB chain was exchanged, little or no binding was observ ed, indicating that specificity of HLA-DQ peptide binding was determin ed by polymorphic residues of both the alpha and beta chains. (3) Unex pectedly, the TfR 215-230 self peptide, eluted from DQ, was promiscuou s with regard to HLA-DR binding. This distinct DR and DQ binding patte rn could reflect the structure of these two molecules as recently evid enced by crystallography.