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[Cancer Research 59, 5554-5559, November 1, 1999]
© 1999 American Association for Cancer Research
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[Cancer Research 59, 5554-5559, November 1, 1999]
© 1999 American Association for Cancer Research

Immunology

The Renal Cell Carcinoma-associated Antigen G250 Encodes a Human Leukocyte Antigen (HLA)-A2.1-restricted Epitope Recognized by Cytotoxic T Lymphocytes1

Joost L. M. Vissers, I. Jolanda M. De Vries, Marco W. J. Schreurs, Linda P. H. Engelen, Egbert Oosterwijk, Carl G. Figdor and Gosse J. Adema2

Tumor Immunology Laboratory [J. L. M. V., I. J. M. D. V., M. W. J. S., L. P. H. E., C. G. F., G. J. A.] and Department of Urology [E. O.], University Hospital Nijmegen St. Radboud, 6525 EX Nijmegen, the Netherlands

Evidence has accumulated that the immune system can play a significant role in the defense against tumors in humans. Especially melanoma and renal cell carcinoma (RCC) are considered immunogenic tumors. In contrast to melanoma, hardly any RCC-associated antigens have been identified as targets for RCC-reactive T cells. Here, we report the identification of a human leukocyte antigen (HLA)-A2.1-restricted T-cell epitope within the G250 antigen. This antigen is expressed in 85% of RCCs but not by neighboring normal kidney tissue and has recently been molecularly defined and shown to be identical to MN/CA IX. Computer-aided motif prediction revealed the presence of 60 potential HLA-A2.1-binding peptides within the G250 antigen. Subsequent binding analysis showed that 13 of these peptides bound to HLA-A2.1 with high-to-intermediate affinity. Analysis of their immunogenicity in HLA-A2.1Kb transgenic mice indicated that 4 of the 13 peptides gave rise to cytotoxic T lymphocytes (CTLs) capable of lysing peptide-loaded target cells. However, only the G250 peptide 254–262 induced CTLs that recognized target cells that endogenously expressed the G250 antigen. Similarly, we were also able to raise human CTLs against the G250 peptide 254–262, which lysed target cells that endogenously expressed the G250 antigen. These findings and the high prevalence of this antigen in RCC patients makes G250 a potential target for anti-RCC immunotherapy.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.