Not All Mismatches Were Created Equal: Empirical Identification of Regions Within HLA-DQ Molecules That Harbor the Highest Immunogenicity

These findings clearly demonstrate that some "molecular mismatches" are more immunogenic than others. They further support our previous observations documenting increased risk of HLA-DQα*05 heterodimer mismatches and provide a tool to continue interrogating differential immunogenicity. Finally, we provide guidance to identify high- and low-risk HLA-DQ mismatches. Taken together, our study supports a different conceptual and experimental framework to study HLA-DQ immunogenicity, and an immunological rationale to guide risk stratification.