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Science 294 (5548): 1936-1939

Copyright © 2001 by the American Association for the Advancement of Science

T Cell Responses Modulated Through Interaction Between CD8alpha alpha and the Nonclassical MHC Class I Molecule, TL

Andrew J. Leishman,1*dagger Olga V. Naidenko,1*ddagger Antoine Attinger,1 Frits Koning,12 Christopher J. Lena,1 Yi Xiong,3 Hsiu-Ching Chang,3 Ellis Reinherz,3 Mitchell Kronenberg,1 Hilde Cheroutre1§

The thymus leukemia antigen (TL) is a nonclassical class I molecule, expressed abundantly on intestinal epithelial cells. We show that, in contrast to other major histocompatibility complex (MHC) class I molecules that bind CD8alpha beta , TL preferentially binds the homotypic form of CD8alpha (CD8alpha alpha ). Thus, TL tetramers react specifically to CD8alpha alpha -expressing cells, including most intestinal intraepithelial lymphocytes. Compared with CD8alpha beta , which recognizes the same MHC as the T cell receptor (TCR) and thus acts as a TCR coreceptor, high-affinity binding of CD8alpha alpha to TL modifies responses mediated by TCR recognition of antigen presented by distinct MHC molecules. These findings define a novel mechanism of lymphocyte regulation through CD8alpha alpha and MHC class I.

1 Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA.
2 Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, Netherlands.
3 Laboratory of Immunobiology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
*   These authors contributed equally to this work.

dagger    Present address: PPL Therapeutics, Roslin, Edinburgh, EH25 9PP, Scotland, UK.

ddagger    Present address: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.

§   To whom correspondence should be addressed. E-mail: hilde{at}liai.org



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