CTL INDUCTION BY A TUMOR-ASSOCIATED ANTIGEN OCTAPEPTIDE DERIVED FROM A MURINE LUNG-CARCINOMA

MANY mouse and human tumours express major histocompatibility complex (MHC) class I-associated antigens that constitute targets for syngenei c cytotoxic T lymphocytes (CTL). Genes encoding such antigens were iso lated from a mouse mastocytoma and from human melanomas by genetic met hods(1,2). Isolation and characterization of MHC class I-associated pe ptides has enabled specific anchor residues to be identified that are typical of peptides that bind to distinct class I molecules(3). Moreov er, CTL specific to particular MHC-peptide combinations have been used to identify naturally occurring antigenic peptides in cell extracts a nd enabled them to be sequenced directly(4-6). Most known MHC ligands are of viral origin or are self peptides derived from normal proteins( 7). Here we use total acid extraction and repeated fractionation to is olate and sequence Lewis lung carcinoma (3LL)-specific peptide(s), whi ch shows sequence homology to the connexin 37 protein. Synthetic octam ers based on these sequences bind to 'empty' H-2K(b) molecules on RMA- S cells, sensitize RMA-S cells to lysis by specific anti-3LL CTL, and induce anti-tumour CTL. The tumour-associated peptide originates from mutated connexin 37 expressed in 3LL.