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Use of selected reaction monitoring mass spectrometry for the detection of specific MHC class I peptide antigens on A3 supertype family members

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Abstract

The development of peptide-based vaccines that are useful in the therapeutic treatment of melanoma and other cancers ultimately requires the identification of a sufficient number of antigenic peptides so that most individuals, regardless of their major histocompatibility complex (MHC)–encoded class I molecule phenotype, can develop a cytotoxic T lymphocyte (CTL) response against one or more peptide components of the vaccine. While it is relatively easy to identify antigenic peptides that are presented by the most prevalent MHC class I molecules in the population, it is problematic to identify antigenic peptides that are presented by MHC class I molecules that have less frequent expression in the population. One manner in which this problem can be overcome is by taking advantage of known MHC class I supertypes, which are groupings of MHC class I molecules that bind peptides sharing a common motif. We have developed a mass spectrometric approach which can be used to determine if an antigenic peptide is naturally processed and presented by any given MHC class I molecule. This approach has been applied to the A3 supertype, and the results demonstrate that some, but not all, A3 supertype family–associated peptides can associate with all A3 supertype family members. The approach also demonstrates the shared nature of several newly identified peptide antigens. The use of this technology negates the need to test peptides for their ability to stimulate CTL responses in those cases where the peptide is not naturally processed and bound to the target MHC class I molecule of interest, thus allowing resources to be focused on the most promising vaccine candidates.

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Acknowledgements

The authors would like to thank Mitsu Fink, Julie Fitzgerald, and Chantel Tracy for their assistance with the cell culture and isolation of the peptides bound to the A3 supertype molecules. This work was supported by RO1CA90815 (KTH), K08CA91995 (KUC), RO1AI33993 (DFH), and RO1CA57653 (CLS).

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Authors and Affiliations

  1. Department of Surgery, University of Virginia, Box 801359, Charlottesville, VA, 22908, USA

    Kevin T. Hogan, Kyo U. Chu & Craig L. Slingluff Jr

  2. Department of Chemistry, University of Virginia, Charlottesville, VA, 22908, USA

    Jennifer N. Sutton, Jennifer A. C. Busby, Jeffrey Shabanowitz & Donald F. Hunt

  3. Department of Pathology, University of Virginia, Charlottesville, VA, 22908, USA

    Donald F. Hunt

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  1. Kevin T. Hogan
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  2. Jennifer N. Sutton
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  3. Kyo U. Chu
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  4. Jennifer A. C. Busby
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  5. Jeffrey Shabanowitz
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  6. Donald F. Hunt
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  7. Craig L. Slingluff Jr
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Correspondence to Kevin T. Hogan.

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Hogan, K.T., Sutton, J.N., Chu, K.U. et al. Use of selected reaction monitoring mass spectrometry for the detection of specific MHC class I peptide antigens on A3 supertype family members. Cancer Immunol Immunother 54, 359–371 (2005). https://doi.org/10.1007/s00262-004-0592-y

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  • DOI: https://doi.org/10.1007/s00262-004-0592-y

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