This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Frassanito, M. A. Articles by DeLeo, A. B. Search for Related Content PubMed PubMed Citation Articles by Frassanito, M. A. Articles by DeLeo, A. B.

Identification of Meth A Sarcoma-derived Class I Major Histocompatibility Complex-associated Peptides Recognized by a Specific CD8⁺ Cytotoxic T Lymphocyte

The Pittsburgh Cancer Institute, Division of Basic Research, and the Departments of Pathology [M. A. F., R. M. D., A. B. D.] and Surgery [J. I. M., W. J. S., M. T. L.], and Molecular Genetics and Biochemistry [W. J. S., M. T. L.], University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261

The finding that class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL) recognize peptide antigens (epitopes) bound to class I MHC molecules has accelerated efforts to identify CTL-defined tumor peptides for the development of peptide-based cancer immunotherapy. The Meth A sarcoma is probably one of the best studied of all murine tumors. It is extremely lethal unless protective immunity is induced. We recently reported the characterization of a cloned H-2K^d-restricted, CD8⁺ anti-Meth A CTL line (CTLMA-9C; Frassanito et al., Cancer Res., 54: 4424–4429, 1994). The cytotoxic reactivity of this CTL was shown to be restricted to Meth A sarcoma, and the results of the analysis of the immunogenicity of the CTL-resistant variant of Meth A, designated Meth A4R, indicate that the CTL-defined epitope is functional in tumor rejection. Here we have isolated class I MHC-associated peptides from Meth A sarcoma by mild acid treatment and resolved them into sixty fractions by reverse phase-HPLC. These fractions were then tested for their ability to sensitize the DBA/2 mastocytoma P815 to cytolysis by the anti-Meth A CTL. A single fraction, fraction 27, has been repeatedly identified as containing the CTL-defined epitope. Peptides eluted from the CTL-resistant variant, Meth A4R, failed to sensitize P815 to cytolysis by the anti-Meth A CTL, while fraction 27 derived from Meth A sensitized Meth A4R to lysis by the CTL. These findings confirm the peptide nature of the epitope recognized by CTL on the surface of Meth A. Our future efforts will focus on the identification and sequence analysis of the tumor peptides and the development of a tumor peptide-based vaccine model for immunotherapy.

¹ To whom request for reprints should be addressed, at Pittsburgh Cancer Institute, Division of Basic Research, Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA 15261.

Received 9/ 1/94. Accepted 11/ 1/94.