Meanwhile, the observation that endogenously expressed TSHR A subunits are in general more efficient than non-cleaving TSHR and wild-type TSHR for inducing TSAb and Graves’ hyperthyroidism in animal models (45) depicts another possible scenario, in which the shed TSHR A subunit might be internalized by MHC class II-positive thyrocytes and presented through the conventional lysosome/endosome-MHC class II pathway. Here, TSHR is linked to Graves disease.