IDENTIFICATION OF SHARED TUMOR-ASSOCIATED ANTIGEN PEPTIDES BETWEEN 2 SPONTANEOUS LUNG CARCINOMAS

CTLs recognize antigenic peptides bound to MHC class I Ags on the cell surface of tumor cells. Tumor-associated Ag (TAA) peptides are 8 to 1 0 amino acids long and can be derived from normal, mutated, or viral p roteins. The majority of T cell-defined Ags have been identified in hu man melanoma tells. These were shown to be commonly expressed by diffe rent allogeneic melanomas that share the same MHC molecule. We have re cently isolated Kb-restricted TAA peptides, which are mutations of the gap junction protein connexin 37, from the spontaneous C57BL/6 Lewis lung carcinoma (3LL). These peptides, named MUT 1 and MUT 2, serve as CTL epitopes and can induce CTL activity in vivo. Using CTL cross-reac tion assays, peptide extraction, HPLC fractionation, and reverse trans criptase-PCR amplification, we show that clones of another spontaneous C57BL/6 lung carcinoma, CMT 64, share TAA peptides with the 3LL carci noma. Vaccination with synthetic MUT 1 or MUT 2 induces CTLs that effi ciently lyse CMT 64-derived clones, protects mice from CMT 64 metastas is, and affords therapy of established CMT 64 metastases. Hence, share d CTL epitopes exist between two spontaneous murine lung carcinomas.