There is a considerable body of evidence that CD8+ T lymphocytes (TCD8+) are induced by tumors and can function to kill tumor cells. Nevertheless, in many cases, tumors obviously overcome any tumor specific TCD8+ response that might be induced following tumor induction, since cancer is a leading cause of death. We are investigating the possibility that in some of these cases, the failure of TCD8+ to prevent malignancies is due to the selection of mutants that are unable to effectively present tumor antigen for recognition by the immune system. In the past few years there has been tremendous progress in our understanding of how cells present antigens for recognition by TCD8+. It is now clear that presentation of antigen results from a chain events including protein breakdown into peptides of 8 to 10 amino acids, transport of peptides from the cytosol to a secretory compartment, binding of peptides to a special peptide-presenting complex, and delivery of the presenting molecule to the cell surface. We devised a rapid and simple method for measuring the ability of tumor cells to present antigens for TCD8+ recognition, and found that a high percentage of human tumors were unable to present antigens to TCD8+. We showed that in at least some cases, this is due to the down regulation of all of the known components of the antigen processing and presentation mechanism, and in others, is due to a selective deficiency in a single molecule that forms part of the final peptide presenting complex.
