GENE-TRANSFER EXPERIMENTS IMPLY INSTRUCTIVE ROLE OF MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I MOLECULES IN CELLULAR PEPTIDE PROCESSING

DBA/2-derived mouse tumor cells were transfected with the H-2 K(b) gene. Naturally processed minor histocompatibility (H) peptides were extracted from both transfected and non-transfected cells by acid elution, and were separated by high-performance liquid chromatography. K(b)-restricted minor H epitopes corresponding to H-4b and mapki, both encoded by non-major histocompatibility complex genes of DBA/2, were readily detected by the respective cytotoxic T lymphocyte in peptides extracted from K(b)-transfected, but not from non-transfected or D(b)-transfected cells. Titration experiments indicated at least 3000-fold less copies of correctly processed K(b)-restricted epitopes in cells without K(b) as compared to cells with K(b). Since we estimate the copy number of K(b)-restricted H-4b epitopes in K(b)-expressing transfectants to be less than 1000 per cell, the pool size of H-4b epitopes correctly processed in the absence of K(b) should be less than 1/3 copy per cell.