Interchain disulfide engineering enables the efficient production of functional HLA-DQ-Fc fusion proteins
HLA-DQ molecules drive unwanted alloimmune responses after solid-organ transplants and several autoimmune diseases, including type 1 diabetes and celiac disease. Biologics with HLA molecules as part of the design are emerging therapeutic options for these allo- and autoimmune conditions. However, the soluble α and β chains of class II HLA molecules do not dimerize efficiently without their transmembrane domains, which hinders their production. In this study, we examined the feasibility of interchain disulfide engineering by introducing paired cysteines to juxtaposed positions in the α and β chains of HLA-DQ7, encoded by HLA-DQA1∗05:01 and HLA-DQB1∗03:01 respectively.
