This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services 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 Röhn, T. A. Articles by Kropshofer, H. Search for Related Content PubMed PubMed Citation Articles by Röhn, T. A. Articles by Kropshofer, H.

A Novel Strategy for the Discovery of MHC Class II–Restricted Tumor Antigens: Identification of a Melanotransferrin Helper T-Cell Epitope

¹ Pharmaceutical Research and ² Roche Center for Medical Genomics, F. Hoffmann La Roche Ltd., Basel, Switzerland; ³ German Cancer Research Center, Skin Cancer Unit; and ⁴ Institute of Transfusion Medicine and Immunology, Mannheim, Germany

Requests for reprints: Harald Kropshofer, Pharmaceutical Research, F. Hoffmann La Roche Ltd., CH-4070 Basel, Switzerland. Phone: 41-61-688-3569; Fax: 41-61-688-3678; E-mail: harald.kropshofer{at}roche.com.

CD4⁺ helper T cells play a critical role in orchestrating host immune responses, including antitumor immunity. The limited availability of MHC class II–associated tumor antigens is still viewed as a major obstacle in the use of CD4⁺ T cells in cancer vaccines. Here, we describe a novel approach for the identification of MHC class II tumor-associated antigens (TAAs). By combining two-dimensional liquid chromatography and nanoelectrospray ionization tandem mass spectrometry, we developed a highly sensitive method for the detection of human leukocyte antigen (HLA)-DR–associated peptides of dendritic cells upon exposure to necrotic tumor cells. This approach led to the identification of a novel MHC class II–restricted TAA epitope derived from melanotransferrin. The epitope stimulated T cells derived from melanoma patients and healthy individuals and displayed promiscuity in HLA-DR restriction. Moreover, the same peptide was also presented by MHC class II–positive melanoma cells. This strategy may contribute to increase the number of tumor epitopes presented by MHC class II molecules and may support the development of more efficacious vaccines against cancer.