Phosphorylated Peptides Are Naturally Processed and Presented by Major Histocompatibility Complex Class I Molecules In Vivo

doi:10.1084/jem.192.12.1755

Published online 18 December 2000.

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© The Rockefeller University Press, 0022-1007/2000/12/1755/ $5.00
The Journal of Experimental Medicine, Volume 192, Number 12, December 18, 2000 1755-1762

Original Article

Phosphorylated Peptides Are Naturally Processed and Presented by Major Histocompatibility Complex Class I Molecules In Vivo

Angela L. Zarling^a, Scott B. Ficarro^d, Forest M. White^d, Jeffrey Shabanowitz^d, Donald F. Hunt^b,d, and Victor H. Engelhard^a,c
^a Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia 22908
^b Department of Pathology, University of Virginia, Charlottesville, Virginia 22908
^c Department of Microbiology, University of Virginia, Charlottesville, Virginia 22908
^d Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901

Correspondence to: Victor H. Engelhard, Beirne Carter Center for Immunology Research, Medical Research Building 4, Box 801386, Charlottesville, VA 22908. Tel:804-924-2423 Fax:804-924-1221 E-mail:vhe{at}virginia.edu.

Posttranslational modification of peptide antigens has beenshown to alter the ability of T cells to recognize major histocompatibilitycomplex (MHC) class I–restricted peptides. However, theexistence and origin of naturally processed phosphorylated peptidespresented by MHC class I molecules have not been explored. Byusing mass spectrometry, significant numbers of naturally processedphosphorylated peptides were detected in association with severalhuman MHC class I molecules. In addition, CD8⁺ T cells couldbe generated that specifically recognized a phosphorylated epitope.Thus, phosphorylated peptides are part of the repertoire ofantigens available for recognition by T cells in vivo.

Key Words: MHC class I, posttranslational protein processing, phosphopeptides,mass spectrometry, cytotoxic T lymphocytes

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