Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 180K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Colella, T. A. Articles by Engelhard, V. H. Search for Related Content PubMed PubMed Citation Articles by Colella, T. A. Articles by Engelhard, V. H. Social Bookmarking                            What's this?

Original Article

Teresa A. Colella^a, Timothy N.J. Bullock^a, Liane B. Russell^b, David W. Mullins^a, Willem W. Overwijk^c, Chance John Luckey^a, Richard A. Pierce^a, Nicholas P. Restifo^c, and Victor H. Engelhard^a

^a Department of Microbiology and the Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia 22908
^b Life Sciences Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee 37831
^c Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892
Department of Microbiology and the Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, VA 22908.804-924-1221804-924-2423

vhe{at}virginia.edu

The human tyrosinase-derived peptide YMDGTMSQV is presented on the surface of human histocompatibility leukocyte antigen (HLA)-A*0201⁺ melanomas and has been suggested to be a tumor antigen despite the fact that tyrosinase is also expressed in melanocytes. To gain information about immunoreactivity and self-tolerance to this antigen, we established a model using the murine tyrosinase-derived homologue of this peptide FMDGTMSQV, together with transgenic mice expressing the HLA-A*0201 recombinant molecule AAD. The murine peptide was processed and presented by AAD similarly to its human counterpart. After immunization with recombinant vaccinia virus encoding murine tyrosinase, we detected a robust AAD-restricted cytotoxic T lymphocyte (CTL) response to FMDGTMSQV in AAD transgenic mice in which the entire tyrosinase gene had been deleted by a radiation-induced mutation. A residual response was observed in the AAD⁺tyrosinase⁺ mice after activation under certain conditions. At least some of these residual CTLs in AAD⁺tyrosinase⁺ mice were of high avidity and induced vitiligo upon adoptive transfer into AAD⁺tyrosinase⁺ hosts. Collectively, these data suggest that FMDGTMSQV is naturally processed and presented in vivo, and that this presentation leads to substantial but incomplete self-tolerance. The relevance of this model to an understanding of the human immune response to tyrosinase is discussed.

Key Words: tyrosinase • self-tolerance • MHC class I • cytotoxic T lymphocytes • immunotherapy

The sequence YMNGTMSQV from the tyrosinase gene was initially identified as residues 368–376 13, and this laboratory had previously used that numbering system 38. The correct numbering for the YMNGTMSQV peptide is 369–377.

© 2000 The Rockefeller University Press

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS