Stable association of protein antigen with MHC class II in an HLA-DM-independent pathway

A partially folded and radioiodinated lysozyme protein HEL) bound to purified I-Ak (=Ak) or to Ak on the surface of antigen presenting cells (APC). The HEL-Ak complex was SDS-unstable despite binding with a strong affinity. However, in the APC the HEL, with time, appeared intracellularly as an SDS-stable complex. The conversion to a stable complex required internalization in acidic vesicles that recycled the complex to the plasma membrane. The change or editing of partially folded protein took place in mature Ak molecules, did not require proteolysis and did not involve HLA-DM. This editing pathway is distinct from that involving the generation of HEL peptides which involves proteolysis, newly synthesized Ak molecules and HLA-DM.