CTL induction by a tumour-associated antigen octapeptide derived from a murine lung carcinoma

Abstract

MANY mouse and human tumours express major histocompatibility complex (MHC) class I-associated antigens that constitute targets for syngeneic cy to toxic T lymphocytes (CTL). Genes encoding such antigens were isolated from a mouse mastocytoma and from human melanomas by genetic methods^1,2. Isolation and charac-terization of MHC class I-associated peptides has enabled specific anchor residues to be identified that are typical of peptides that bind to distinct class I molecules³. Moreover, CTL specific to particular MHC-peptide combinations have been used to identify naturally occurring antigenic peptides in cell extracts and enabled them to be sequenced directly^4–6. Most known MHC ligands are of viral origin or are self peptides derived from normal proteins⁷. Here we use total acid extraction and repeated fractionation to isolate and sequence Lewis lung carcinoma (3LL)-specific pep-tide(s), which shows sequence homology to the connexin 37 protein. Synthetic octamers 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.s