Natural Killer T cells Balancing the Regulation of Tumor Immunity
Natural killer T (NKT) cells are CD1d-restricted T cells that respond to lipid, not protein, antigens presented by CD1d, which is a non-classical MHC class I-like molecule. This relatively small but pivotal T cell population bridges the gap between
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Series Editor Beverly A. Teicher Genzyme Corporation, Framington, MA, USA
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-ASAKI4ERABE s *AY!"ERZOFSKY Editors
Natural Killer T cells Balancing the Regulation of Tumor Immunity
Editors Masaki Terabe Vaccine Branch National Cancer Institute, National Institute of Health Bethesda, MD 20892 USA [email protected]
*AY!"ERZOFSKY Vaccine Branch National Cancer Institute, National Institute of Health Bethesda, MD 20892 USA [email protected]
ISBN 978-1-4614-0612-9 e-ISBN 978-1-4614-0613-6 DOI 10.1007/978-1-4614-0613-6 Springer New York Dordrecht Heidelberg London Library of Congress Control Number: 2011935528 © Springer Science+Business Media, LLC 2012 All rights reserved. This work may not be translated or copied in whole or in part without the written permission of the publisher (Springer Science+Business Media, LLC, 233 Spring Street, New York, NY 10013, USA), except for brief excerpts in connection with reviews or scholarly analysis. Use in connection with any form of information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed is forbidden. The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are not identified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietary rights. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)
Preface
Natural killer T (NKT) cells discussed in this book are CD1d-restricted T cells, not to be confused with NK cells. Unlike conventional T cells restricted by conventional class I or II major histocompatibility complex (MHC) antigens, they respond to antigens presented by CD1d, which is a non-classical MHC class I-like molecule. It has been two decades since NKT cells were first identified as NK1.1 expressing T cells. One of the highlights of the early discoveries on NKT cells is the identification of their unique TCR gene segment usage, namely VD*D281 (now called VD*D18), forming an invariant TCR alpha chain (now these NKT cells are called type I NKT cells or iNKT cells) and its prototypic agonistic antigen alpha-galactosylceramide (KRN7000). This stunning finding shed light on some important characteristics of this relatively small but pivotal T cell population. First, NKT cells recognize lipid, not protein, antigens, indicating that this T cell subset surveys a range of antigens distinct from that of conventional T cells. Given that lipids are major components of any cells or viruses, it makes sense the immune system has a T cell repertoire that surveys lipids. Second, despite the fact that NKT cells are only approximately 1% of mouse spleen cells, they can strongly regulate tumor immunity. Third, because of the expression of the invariant TCR alpha chain, one can stimulate most type I NKT cells with a single antigen such as KRN7000. Overall, NKT cells bridge the gap between the in
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