DIFFERENT MODES OF PEPTIDE INTERACTION ENABLE HLA-DQ AND HLA-DR MOLECULES TO BIND DIVERSE PEPTIDE REPERTOIRES

The role of HLA-DQ molecules in eg presentation has, thus far, remaine d elusive. Here we report that two DQ allotypes, DQ7 (DQA10501/B1*030 1) and DQ9 (DQA10201/B1*0303), are capable of binding peptide reperto ires in complementarity with DR molecules. The results reflect fundame ntal differences in the binding modes of these two HLA class II isotyp es, in that DQ7 and DQ9 but not DR molecules appear to have the capaci ty to bind peptide structures without type 1-like anchor residues. Con sistent with this is our observation that none of the amino acid side chains of the class Ii-associated invariant chain peptides (CLIP) are required for association with DQ7 and DQ9, even though many of them ar e essential for CLIP-DR interaction. Together, these data reveal a fun ctional complementarity of HLA-DR and -DQ molecules in Ag presentation .