Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 30 November 2001:
Vol. 294. no. 5548, pp. 1936 - 1939
DOI: 10.1126/science.1063564
Prev | Table of Contents | Next

Reports

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

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
CD4 and CD8: an inside-out coreceptor model for innate immune cells.
D. Gibbings and A. D. Befus (2009)
J. Leukoc. Biol. 86, 251-259
   Abstract »    Full Text »    PDF »
Dendritic Cells Use Endocytic Pathway for Cross-Priming Class Ib MHC-Restricted CD8{alpha}{alpha}+TCR{alpha}{beta}+ T Cells with Regulatory Properties.
T. R. F. Smith, X. Tang, I. Maricic, Z. Garcia, S. Fanchiang, and V. Kumar (2009)
J. Immunol. 182, 6959-6968
   Abstract »    Full Text »    PDF »
Uneven Colonization of the Lymphoid Periphery by T Cells That Undergo Early TCR{alpha} Rearrangements.
D. W. Hendricks and P. J. Fink (2009)
J. Immunol. 182, 4267-4274
   Abstract »    Full Text »    PDF »
An Essential Role for the Stalk Region of CD8{beta} in the Coreceptor Function of CD8.
L. Rettig, L. McNeill, N. Sarner, P. Guillaume, I. Luescher, M. Tolaini, D. Kioussis, and R. Zamoyska (2009)
J. Immunol. 182, 121-129
   Abstract »    Full Text »    PDF »
Thymus leukemia antigen controls intraepithelial lymphocyte function and inflammatory bowel disease.
D. Olivares-Villagomez, Y. V. Mendez-Fernandez, V. V. Parekh, S. Lalani, T. L. Vincent, H. Cheroutre, and L. Van Kaer (2008)
PNAS 105, 17931-17936
   Abstract »    Full Text »    PDF »
Evidence That CD8+ Dendritic Cells Enable the Development of {gamma}{delta} T Cells That Modulate Airway Hyperresponsiveness.
L. Cook, N. Miyahara, N. Jin, J. M. Wands, C. Taube, C. L. Roark, T. A. Potter, E. W. Gelfand, R. L. O'Brien, and W. K. Born (2008)
J. Immunol. 181, 309-319
   Abstract »    Full Text »    PDF »
Kinetics of MHC-CD8 Interaction at the T Cell Membrane.
J. Huang, L. J. Edwards, B. D. Evavold, and C. Zhu (2007)
J. Immunol. 179, 7653-7662
   Abstract »    Full Text »    PDF »
Different T Cell Receptor Affinity Thresholds and CD8 Coreceptor Dependence Govern Cytotoxic T Lymphocyte Activation and Tetramer Binding Properties.
B. Laugel, H. A. van den Berg, E. Gostick, D. K. Cole, L. Wooldridge, J. Boulter, A. Milicic, D. A. Price, and A. K. Sewell (2007)
J. Biol. Chem. 282, 23799-23810
   Abstract »    Full Text »    PDF »
CD8 Raft Localization Is Induced by Its Assembly into CD8{alpha}beta Heterodimers, Not CD8{alpha}{alpha} Homodimers.
D. J. Pang, A. C. Hayday, and M.-J. Bijlmakers (2007)
J. Biol. Chem. 282, 13884-13894
   Abstract »    Full Text »    PDF »
The same genomic region conditions clonal deletion and clonal deviation to the CD8{alpha}{alpha} and regulatory T cell lineages in NOD versus C57BL/6 mice.
P. D. Holler, T. Yamagata, W. Jiang, M. Feuerer, C. Benoist, and D. Mathis (2007)
PNAS 104, 7187-7192
   Abstract »    Full Text »    PDF »
Genomic Organization of the Chicken CD8 Locus Reveals a Novel Family of Immunoreceptor Genes.
H.-J. Liaw, W.-R. Chen, Y.-C. Huang, C.-W. Tsai, K.-C. Chang, and C.-L. Kuo (2007)
J. Immunol. 178, 3023-3030
   Abstract »    Full Text »    PDF »
Influence of Human CD8 on Antigen Recognition by T-Cell Receptor-Transduced Cells.
G. E. Lyons, T. Moore, N. Brasic, M. Li, J. J. Roszkowski, and M. I. Nishimura (2006)
Cancer Res. 66, 11455-11461
   Abstract »    Full Text »    PDF »
Mapping the Binding Site on CD8beta for MHC Class I Reveals Mutants with Enhanced Binding.
L. Devine, D. Thakral, S. Nag, J. Dobbins, M. E. Hodsdon, and P. B. Kavathas (2006)
J. Immunol. 177, 3930-3938
   Abstract »    Full Text »    PDF »
CD8{alpha}{alpha}-Mediated Intraepithelial Lymphocyte Snatching of Thymic Leukemia MHC Class Ib Molecules In Vitro and In Vivo.
N. Pardigon, K. Takeda, B. Saunier, F. Hornung, J. Gibbs, A. Weisberg, N. Contractor, B. Kelsall, J. R. Bennink, and J. W. Yewdell (2006)
J. Immunol. 177, 1590-1598
   Abstract »    Full Text »    PDF »
Circulating {gamma}{delta} T Cells in Response to Salmonella enterica Serovar Enteritidis Exposure in Chickens.
A. Berndt, J. Pieper, and U. Methner (2006)
Infect. Immun. 74, 3967-3978
   Abstract »    Full Text »    PDF »
Loss of CD8 and TCR binding to Class I MHC ligands following T cell activation.
C. Kao, M. A. Daniels, and S. C. Jameson (2005)
Int. Immunol. 17, 1607-1617
   Abstract »    Full Text »    PDF »
Cutting Edge: Memory CD8 T Cell Maturation Occurs Independently of CD8{alpha}{alpha}.
A. Chandele and S. M. Kaech (2005)
J. Immunol. 175, 5619-5623
   Abstract »    Full Text »    PDF »
The Murine Family of Gut-Restricted Class Ib MHC Includes Alternatively Spliced Isoforms of the Proposed HLA-G Homolog, "Blastocyst MHC".
P. A. Guidry and I. Stroynowski (2005)
J. Immunol. 175, 5248-5259
   Abstract »    Full Text »    PDF »
Human Immunodeficiency Virus Nef Induces Rapid Internalization of the T-Cell Coreceptor CD8{alpha}{beta}.
V. Stove, I. Van de Walle, E. Naessens, E. Coene, C. Stove, J. Plum, and B. Verhasselt (2005)
J. Virol. 79, 11422-11433
   Abstract »    Full Text »    PDF »
Molecular Basis for the High Affinity Interaction between the Thymic Leukemia Antigen and the CD8{alpha}{alpha} Molecule.
A. Attinger, L. Devine, Y. Wang-Zhu, D. Martin, J.-h. Wang, E. L. Reinherz, M. Kronenberg, H. Cheroutre, and P. Kavathas (2005)
J. Immunol. 174, 3501-3507
   Abstract »    Full Text »    PDF »
The Role of CTLs in Persistent Viral Infection: Cytolytic Gene Expression in CD8+ Lymphocytes Distinguishes between Individuals with a High or Low Proviral Load of Human T Cell Lymphotropic Virus Type 1.
A. M. Vine, A. G. Heaps, L. Kaftantzi, A. Mosley, B. Asquith, A. Witkover, G. Thompson, M. Saito, P. K. C. Goon, L. Carr, et al. (2004)
J. Immunol. 173, 5121-5129
   Abstract »    Full Text »    PDF »
Fas-Fas Ligand Interactions Are Essential for the Binding to and Killing of Activated Macrophages by {gamma}{delta} T Cells.
J. E. Dalton, G. Howell, J. Pearson, P. Scott, and S. R. Carding (2004)
J. Immunol. 173, 3660-3667
   Abstract »    Full Text »    PDF »
The TL MHC class Ib molecule has only marginal effects on the activation, survival and trafficking of mouse small intestinal intraepithelial lymphocytes.
N. Pardigon, S. Darche, B. Kelsall, J. R. Bennink, and J. W. Yewdell (2004)
Int. Immunol. 16, 1305-1313
   Abstract »    Full Text »    PDF »
CD4-CD8{alpha}{alpha} Subset of CD1d-Restricted NKT Cells Controls T Cell Expansion.
L.-P. Ho, B. C. Urban, L. Jones, G. S. Ogg, and A. J. McMichael (2004)
J. Immunol. 172, 7350-7358
   Abstract »    Full Text »    PDF »
Infection-Induced Expansion of a MHC Class Ib-Dependent Intestinal Intraepithelial {gamma}{delta} T Cell Subset.
A. Davies, S. Lopez-Briones, H. Ong, C. O'Neil-Marshall, F. A. Lemonnier, K. Nagaraju, E. S. Metcalf, and M. J. Soloski (2004)
J. Immunol. 172, 6828-6837
   Abstract »    Full Text »    PDF »
CD8{alpha}{alpha}-Mediated Survival and Differentiation of CD8 Memory T Cell Precursors.
L. T. Madakamutil, U. Christen, C. J. Lena, Y. Wang-Zhu, A. Attinger, M. Sundarrajan, W. Ellmeier, M. G. von Herrath, P. Jensen, D. R. Littman, et al. (2004)
Science 304, 590-593
   Abstract »    Full Text »    PDF »
Virus-Induced Activation of Self-Specific TCR{alpha}{beta} CD8{alpha}{alpha} Intraepithelial Lymphocytes Does Not Abolish Their Self-Tolerance in the Intestine.
L. Saurer, I. Seibold, S. Rihs, C. Vallan, T. Dumrese, and C. Mueller (2004)
J. Immunol. 172, 4176-4183
   Abstract »    Full Text »    PDF »
Thymus leukemia antigen (TL)-specific cytotoxic T lymphocytes recognize the {alpha}1/{alpha}2 domain of TL free from antigenic peptides.
K. Tsujimura, Y. Obata, E. Kondo, K. Nishida, Y. Matsudaira, Y. Akatsuka, K. Kuzushima, and T. Takahashi (2003)
Int. Immunol. 15, 1319-1326
   Abstract »    Full Text »    PDF »
Clonal Expansion of Double-Positive Intraepithelial Lymphocytes by MHC Class I-Related Chain A Expressed in Mouse Small Intestinal Epithelium.
E. J. Park, I. Takahashi, J. Ikeda, K. Kawahara, T. Okamoto, M.-N. Kweon, S. Fukuyama, V. Groh, T. Spies, Y. Obata, et al. (2003)
J. Immunol. 171, 4131-4139
   Abstract »    Full Text »    PDF »
Gene expression analysis of thymocyte selection in vivo.
I. Schmitz, L. K. Clayton, and E. L. Reinherz (2003)
Int. Immunol. 15, 1237-1248
   Abstract »    Full Text »    PDF »
Species-Specific Class I Gene Expansions Formed the Telomeric 1 Mb of the Mouse Major Histocompatibility Complex.
T. Takada, A. Kumanovics, C. Amadou, M. Yoshino, E. P. Jones, M. Athanasiou, G. A. Evans, and K. F. Lindahl (2003)
Genome Res. 13, 589-600
   Abstract »    Full Text »    PDF »
Hyperconservation of the Putative Antigen Recognition Site of the MHC Class I-b Molecule TL in the Subfamily Murinae: Evidence That Thymus Leukemia Antigen Is an Ancient Mammalian Gene.
B. K. Davis, R. G. Cook, R. R. Rich, and J. R. Rodgers (2002)
J. Immunol. 169, 6890-6899
   Abstract »    Full Text »    PDF »
In Vivo Evidence for Interferon-gamma -mediated Homeostatic Mechanisms in Small Intestine of the NHE3 Na+/H+ Exchanger Knockout Model of Congenital Diarrhea.
A. L. Woo, L. A. Gildea, L. M. Tack, M. L. Miller, Z. Spicer, D. E. Millhorn, F. D. Finkelman, D. J. Hassett, and G. E. Shull (2002)
J. Biol. Chem. 277, 49036-49046
   Abstract »    Full Text »    PDF »
Peptide-Independent Folding and CD8{alpha}{alpha} Binding by the Nonclassical Class I Molecule, Thymic Leukemia Antigen.
D. A. Weber, A. Attinger, C. C. Kemball, J. L. Wigal, J. Pohl, Y. Xiong, E. L. Reinherz, H. Cheroutre, M. Kronenberg, and P. E. Jensen (2002)
J. Immunol. 169, 5708-5714
   Abstract »    Full Text »    PDF »
Most Murine CD8+ Intestinal Intraepithelial Lymphocytes Are Partially But Not Fully Activated T Cells.
H.-C. Wang, Q. Zhou, J. Dragoo, and J. R. Klein (2002)
J. Immunol. 169, 4717-4722
   Abstract »    Full Text »    PDF »
The Complementarity-Determining Region-Like Loops of CD8{alpha} Interact Differently with {beta}2-Microglobulin of the Class I Molecules H-2Kb and Thymic Leukemia Antigen, While Similarly with Their {alpha}3 Domains.
L. Devine, L. Rogozinski, O. V. Naidenko, H. Cheroutre, and P. B. Kavathas (2002)
J. Immunol. 168, 3881-3886
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)