Free ligand-induced dissociation of MHC-antigen complexes.

We have analyzed the stability of Ag-class II complexes on the surface of live APC. It was found that the disappearance of complexes formed by I-Ed and the hen egg lysozyme 107-116 peptide is twice as rapid on the surface of live, as compared to glutaraldehyde-fixed APC. Moreover, the addition of peptides with a high affinity for I-Ed could reduce the half-life of Ag-class II complexes on either live or fixed APC. The same effect was detectable using purified class II molecules adhered on plastic microtiter wells, and even in the case of complexes formed in vitro between radiolabeled Ag and purified class II molecules. This effect of accelerated dissociation appeared to be specific because only I-Ed binding peptides were able to accelerate the dissociation of the hen egg lysozyme 107-116/I-Ed complex either on the surface of cells or in purified form in solution, and high affinity I-Ed binders did not affect the half-life of purified OVA 323-339/I-Ad complexes. These results demonstrate that free ligand can influence the kinetics of dissociation of class II-peptide complexes, and therefore suggest that a mechanism other than the classical first order kinetics may be involved in this process.