Mass spectrometric identification of a naturally processed melanoma peptide recognized by CD8+ cytotoxic T lymphocytes

Chiara Castelli, Walter J. Storkus, Markus J. Maeurer, Dina M. Martin, Eric C. Huang, Birendra N. Pramanik, Tattanahalli L. Nagabhushan, Giorgio Parmiani, Michael T. Lotze

Research output: Contribution to journalArticle

Abstract

We and others have previously reported that melanoma-specific, cytotoxic T lymphocytes (CTL) define a minimum of six class I-presented peptide epitopes common to most HLA-A2 melanomas. Here we show that three of these peptide epitopes are coordinately recognized by a CTL clone obtained by limiting dilution from the peripheral blood of an HLA-A2+ melanoma patient. Tandem mass spectrometry was used to characterize and sequence one of these three naturally processed melanoma peptides. One of the potential forms of the deduced peptide sequence (XXTVXXGVX, X = I or L) matches positions 32-40 of the recently identified melanoma gene MART-1/Melan-A. This peptide (p939; ILTVILGVL) binds to HLA-A2 with an intermediate-to-low affinity and is capable of sensitizing the HLA-A2+ T2 cell line to lysis by CTL lines and clones derived from five different melanoma patients. A relative high frequency of anti-p939-specific effector cells appear to be present in situ in HLA-A2+ melanoma patients, since p939 is also recognized by freshly isolated tumor infiltrating lymphocytes. p939 represents a good candidate for the development of peptide-based immunotherapies for the treatment of patients with melanoma.

Original languageEnglish
Pages (from-to)363-368
Number of pages6
JournalJournal of Experimental Medicine
Volume181
Issue number1
DOIs
Publication statusPublished - Jan 1 1995

ASJC Scopus subject areas

  • Immunology

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    Castelli, C., Storkus, W. J., Maeurer, M. J., Martin, D. M., Huang, E. C., Pramanik, B. N., Nagabhushan, T. L., Parmiani, G., & Lotze, M. T. (1995). Mass spectrometric identification of a naturally processed melanoma peptide recognized by CD8+ cytotoxic T lymphocytes. Journal of Experimental Medicine, 181(1), 363-368. https://doi.org/10.1084/jem.181.1.363