DEFECTIVE PROCESSING AND PRESENTATION OF EXOGENOUS ANTIGENS IN MUTANTS WITH NORMAL HLA CLASS-II GENES

PRESENTATION of an exogenous protein antigen to helper (CD4+) T-lymphocytes by antigen presenting cells (APC) generally requires that the APCs degrade the native protein antigen into an immunogenic peptide, a process termed 'antigen processing', and that this peptide bind to a major histocompatibility complex (MHC) class II molecule1-3. The complex of peptide and MHC molecule on the APC surface provides the stimulatory ligand for the αβJ T cell receptor4. The intracellular pathways and molecular mechanisms involved in the generation of the peptide-MHC complex are not well understood. Here, we describe several mutant APCs which are altered in their ability to present native exogenous protein antigens but effectively present immunogenic peptides derived from these proteins. The lesions in these mutants are not in the class II structural genes, but they affect the conformation of mature class II dimers. © 1990 Nature Publishing Group.