HLA-C and autoimmune disease: The third hypothesis is that the conformation of the APLs can trigger the activation of type-B T cells in the periphery without antigen processing by APC, leading to the onset of autoimmune diseases.64, 86, 123 Because APLs, while binding to MHC-II, can have a different hydrogen bonding scheme than those of parent antigenic peptides, these resulting structural differences increase the number of MHC complexes on the surface of the APC.118, 124 As a result, the increase in APL loading on MHC-II can interfere with both TCR binding and T cell stimulation.