Tumor-specific antigens revisited: presentation to the immune system of fusion peptides resulting solely from tumor-specific chromosomal translocations.

Adaptive immune responses depend upon recognition by lymphocytes-T of short polypeptide sequences bound to major histocompatibility complex (MHC) molecules. Since endogenous intracellular proteins can be presented to the immune system in this way, any tumor-specific structure may function as a potentially tumor-specific antigen. Fusion proteins arising as a result of chromosomal translocations provide good candidates for novel tumor-specific antigens recognizable by the host immune system. Recent molecular cloning data have demonstrated the existence of mRNAs encoding several different potential tumor-specific fusion proteins in both acute and chronic leukemias, and analysis of a number of these sequences suggests the presence of a newly defined amino acid motif associated with MHC-binding and T cell recognition. Preliminary data suggest the possibility of generating in vitro lymphocyte-T responses to synthetic peptides representing the chimeric sequences. It remains to be seen whether tumor cells themselves can be recognized by lymphocytes-T in vitro and in vivo, and, if so, how leukemia cells escape such immune surveillance in vivo.