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

This Article Full Text Full Text (PDF, 78K) 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 Jäger, E. Articles by Knuth, A. Search for Related Content PubMed PubMed Citation Articles by Jäger, E. Articles by Knuth, A. Social Bookmarking                            What's this?

Brief Definitive Reports

Elke Jäger^*, Yao-Tseng Chen^,, Jan W. Drijfhout^||, Julia Karbach^*, Mark Ringhoffer^*, Dirk Jäger^*, Michael Arand^¶, Hisashi Wada, Yuji Noguchi, Elisabeth Stockert, Lloyd J. Old, and Alexander Knuth^*

From the ^* II. Medizinische Klinik, Hämatologie–Onkologie, Krankenhaus Nordwest, 60488 Frankfurt, Germany; Cornell University Medical College, New York 10021; Ludwig Institute for Cancer Research, New York Branch at Memorial Sloan-Kettering Cancer Center, New York 10021; ^|| Department of Immunohaematology and Blood Bank, Leiden University Hospital, 2300 Leiden, The Netherlands; and ^¶ Institut für Toxikologie, Johannes Gutenberg Universität, 55131 Mainz, Germany

A growing number of human tumor antigens have been described that can be recognized by cytotoxic T lymphocytes (CTLs) in a major histocompatibility complex (MHC) class I–restricted fashion. Serological screening of cDNA expression libraries, SEREX, has recently been shown to provide another route for defining immunogenic human tumor antigens. The detection of antibody responses against known CTL-defined tumor antigens, e.g., MAGE-1 and tyrosinase, raised the question whether antibody and CTL responses against a defined tumor antigen can occur simultaneously in a single patient. In this paper, we report on a melanoma patient with a high-titer antibody response against the "cancer–testis" antigen NY-ESO-1. Concurrently, a strong MHC class I–restricted CTL reactivity against the autologous NY-ESO-1–positive tumor cell line was found. A stable CTL line (NW38-IVS-1) was established from this patient that reacted with autologous melanoma cells and with allogeneic human histocompatibility leukocyte antigen (HLA)-A2^–, NY-ESO-1–positive, but not NY-ESO-1–negative, melanoma cells. Screening of NY-ESO-1 transfectants with NW38-IVS-1 revealed NY-ESO-1 as the relevant CTL target presented by HLA-A2. Computer calculation identified 26 peptides with HLA-A2–binding motifs encoded by NY-ESO-1. Of these, three peptides were efficiently recognized by NW38-IVS-1. Thus, we show that antigen-specific humoral and cellular immune responses against human tumor antigens may occur simultaneously. In addition, our analysis provides a general strategy for identifying the CTL-recognizing peptides of tumor antigens initially defined by autologous antibody.

This work was partially funded by Krebs forschung Rhein Main and Ludwig Institute for Cancer Research.

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

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS