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 Kb 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. Kb-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 Kb-transfected, but not from non-transfected or Db-transfected cells. Titration experiments indicated at least 3000-fold less copies of correctly processed Kb-restricted epitopes in cells without Kb as compared to cells with Kb. Since we estimate the copy number of Kb-restricted H-4b epitopes in Kb-expressing transfectants to be less than 1000 per cell, the pool size of H-4b epitopes correctly processed in the absence of Kb should be less than 1/3 copy per cell.