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.
Antigen Recognition Determinants of T Cell Receptors
Sunny Shin,1
Ramy El-Diwany,1,2
Steven Schaffert,1
Erin J. Adams,1,2
K. Christopher Garcia,1,2
Pablo Pereira,3
Yueh-hsiu Chien1,2*
Abstract:
The molecular basis of T cell receptor (TCR) recognition ispoorly understood. Here, we analyze the TCR sequences of a natural T cell population specific for the major histocompatibilitycomplex class Ib molecule T22. We find that T22 recognitioncorrelates strongly with a somatically recombined TCR complementarity-determiningregion 3 (CDR3) motif derived from germ lineencoded residues.Sequence diversity around these residues modulates TCR ligand-bindingaffinities, whereas V gene usage correlates mainly with tissueorigin. These results show how an antigen-specific TCR repertoirecan be generated at a high frequency and suggest that T cellsrecognize a limited number of antigens.
1 Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. 2 Department of Program in Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA. 3 Unité du Développement des Lymphocytes, Centre National de la Recherche Scientifique, Unité de Recherche Associée 1961, Institut Pasteur, 75724 Paris, France.
* To whom correspondence should be addressed. E-mail: chien{at}stanford.edu
The editors suggest the following Related Resources on Science sites:
In Science Magazine
PERSPECTIVES
David N. Garboczi (8 April 2005) Science308 (5719), 209.
[DOI: 10.1126/science.1111657] |Summary »|Full Text »|PDF »
Target Specificity of an Autoreactive Pathogenic Human {gamma}{delta}-T Cell Receptor in Myositis.
J. Bruder, K. Siewert, B. Obermeier, J. Malotka, P. Scheinert, J. Kellermann, T. Ueda, R. Hohlfeld, and K. Dornmair (2012)
J. Biol. Chem.
287, 20986-20995
|Abstract »|Full Text »|PDF »
{gamma}{delta} T Cell Receptors Recognize the Non-classical Major Histocompatibility Complex (MHC) Molecule T22 via Conserved Anchor Residues in a MHC Peptide-like Fashion.
A. Sandstrom, L. Scharf, G. McRae, A. J. Hawk, S. C. Meredith, and E. J. Adams (2012)
J. Biol. Chem.
287, 6035-6043
|Abstract »|Full Text »|PDF »
An MHC Class Ib-Restricted CD8+ T Cell Response to Lymphocytic Choriomeningitis Virus.
L. Chen, D. C. Jay, J. D. Fairbanks, X. He, and P. E. Jensen (2011)
J. Immunol.
187, 6463-6472
|Abstract »|Full Text »|PDF »
Flanking V and J Sequences of Complementary Determining Region 3 of T Cell Receptor (TCR) {delta}1 (CDR3{delta}1) Determine the Structure and Function of TCR{gamma}4{delta}1.
Y. Jiang, Y. Guo, X. Xi, L. Cui, and W. He (2011)
J. Biol. Chem.
286, 25611-25619
|Abstract »|Full Text »|PDF »
Evolution of the V, D, and J gene segments used in the primate {gamma}{delta} T-cell receptor reveals a dichotomy of conservation and diversity.
IL-17 Regulates Adipogenesis, Glucose Homeostasis, and Obesity.
L. A. Zuniga, W.-J. Shen, B. Joyce-Shaikh, E. A. Pyatnova, A. G. Richards, C. Thom, S. M. Andrade, D. J. Cua, F. B. Kraemer, and E. C. Butcher (2010)
J. Immunol.
185, 6947-6959
|Abstract »|Full Text »|PDF »
V{gamma}2V{delta}2 T Cell Receptor Recognition of Prenyl Pyrophosphates Is Dependent on All CDRs.
Evidence for a functional sidedness to the {alpha}{beta}TCR.
M. S. Kuhns, A. T. Girvin, L. O. Klein, R. Chen, K. D. C. Jensen, E. W. Newell, J. B. Huppa, B. F. Lillemeier, M. Huse, Y.-h. Chien, et al. (2010)
PNAS
107, 5094-5099
|Abstract »|Full Text »|PDF »
Antigen Specificity of {gamma}{delta} T Cells Depends Primarily on the Flanking Sequences of CDR3{delta}.
X. Xi, Y. Guo, H. Chen, C. Xu, H. Zhang, H. Hu, L. Cui, D. Ba, and W. He (2009)
J. Biol. Chem.
284, 27449-27455
|Abstract »|Full Text »|PDF »
Cutting Edge: {gamma}{delta} Intraepithelial Lymphocytes of the Small Intestine Are Not Biased toward Thymic Antigens.
K. D. C. Jensen, S. Shin, and Y.-h. Chien (2009)
J. Immunol.
182, 7348-7351
|Abstract »|Full Text »|PDF »
{gamma}{delta} T Lymphocyte Homeostasis Is Negatively Regulated by {beta}2-Microglobulin.
J. D. French, C. L. Roark, W. K. Born, and R. L. O'Brien (2009)
J. Immunol.
182, 1892-1900
|Abstract »|Full Text »|PDF »
TNF-{alpha} Is a Positive Regulatory Factor for Human V{gamma}2V{delta}2 T Cells.
Exacerbation of Collagen-Induced Arthritis by Oligoclonal, IL-17-Producing {gamma}{delta} T Cells.
C. L. Roark, J. D. French, M. A. Taylor, A. M. Bendele, W. K. Born, and R. L. O'Brien (2007)
J. Immunol.
179, 5576-5583
|Abstract »|Full Text »|PDF »
Depletion of {gamma}{delta} T Cells Exacerbates Murine Adriamycin Nephropathy.
H. Wu, Y. M. Wang, Y. Wang, M. Hu, G. Y. Zhang, J. F. Knight, D. C.H. Harris, and S. I. Alexander (2007)
J. Am. Soc. Nephrol.
18, 1180-1189
|Abstract »|Full Text »|PDF »
Comparative gene expression by WC1+ {gamma}{delta} and CD4+ {alpha}{beta} T lymphocytes, which respond to Anaplasma marginale, demonstrates higher expression of chemokines and other myeloid cell-associated genes by WC1+ {gamma}{delta} T cells..
K. K. Lahmers, J. F. Hedges, M. A. Jutila, M. Deng, M. S. Abrahamsen, and W. C. Brown (2006)
J. Leukoc. Biol.
80, 939-952
|Abstract »|Full Text »|PDF »
Professional Antigen-Presentation Function by Human {gamma}{delta} T Cells.