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.


Logo for

Science 308 (5719): 227-231

Copyright © 2005 by the American Association for the Advancement of Science

Structure of a {gamma}{delta} T Cell Receptor in Complex with the Nonclassical MHC T22

Erin J. Adams,1,2,3 Yueh-Hsiu Chien,1,3 K. Christopher Garcia1,2,3*

Abstract: {gamma}{delta} T cell receptors (TCRs), {alpha}ß TCRs, and antibodies are the three lineages of somatically recombined antigen receptors. The structural basis for ligand recognition is well defined for {alpha}ß TCR and antibodies but is lacking for {gamma}{delta} TCRs. We present the 3.4 Å structure of the murine {gamma}{delta} TCR G8 bound to its major histocompatibility complex (MHC) class Ib ligand, T22. G8 predominantly uses germline-encoded residues of its {delta} chain complementarity-determining region 3 (CDR3) loop to bind T22 in an orientation substantially different from that seen in {alpha}ß TCR/peptide-MHC. That junctionally encoded G8 residues play an ancillary role in binding suggests a fusion of innate and adaptive recognition strategies.

1 Department of Microbiology and Immunology
2 Department of Structural Biology
3 Program in Immunology, Stanford University School of Medicine, Fairchild D319, 299 Campus Drive, Stanford, CA 94035–5124, USA.

* To whom correspondence should be addressed. E-mail: kcgarcia{at}

Duality of the murine CD8 compartment.
R. Genolet, J. Leignadier, M. Osteras, L. Farinelli, B. J. Stevenson, and I. F. Luescher (2014)
PNAS 111, E1007-E1015
   Abstract »    Full Text »    PDF »
A Novel T Cell Subset with Trans-Rearranged V{gamma}-C{beta} TCRs Shows V{beta} Expression Is Dispensable for Lineage Choice and MHC Restriction.
S. Bowen, P. Sun, F. Livak, S. Sharrow, and R. J. Hodes (2014)
J. Immunol. 192, 169-177
   Abstract »    Full Text »    PDF »
Identification of a New Tuberculosis Antigen Recognized by {gamma}{delta} T Cell Receptor.
X. Xi, X. Han, L. Li, and Z. Zhao (2013)
Clin. Vaccine Immunol. 20, 530-539
   Abstract »    Full Text »    PDF »
Crystal Structure of the Cowpox Virus-Encoded NKG2D Ligand OMCP.
E. Lazear, L. W. Peterson, C. A. Nelson, and D. H. Fremont (2013)
J. Virol. 87, 840-850
   Abstract »    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 »
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.
A. R. Kazen and E. J. Adams (2011)
PNAS 108, E332-E340
   Abstract »    Full Text »    PDF »
Molecular identification of an MHC-independent ligand recognized by a human {alpha}/{beta} T-cell receptor.
K.-i. Hanada, Q. J. Wang, T. Inozume, and J. C. Yang (2011)
Blood 117, 4816-4825
   Abstract »    Full Text »    PDF »
Crystal structure of a {gamma}{delta} T-cell receptor specific for the human MHC class I homolog MICA.
B. Xu, J. C. Pizarro, M. A. Holmes, C. McBeth, V. Groh, T. Spies, and R. K. Strong (2011)
PNAS 108, 2414-2419
   Abstract »    Full Text »    PDF »
Distinctive CD3 Heterodimeric Ectodomain Topologies Maximize Antigen-Triggered Activation of {alpha}{beta} T Cell Receptors.
S. T. Kim, M. Touma, K. Takeuchi, Z.-Y. J. Sun, V. P. Dave, D. J. Kappes, G. Wagner, and E. L. Reinherz (2010)
J. Immunol. 185, 2951-2959
   Abstract »    Full Text »    PDF »
A structural basis for antigen recognition by the T cell-like lymphocytes of sea lamprey.
L. Deng, C. A. Velikovsky, G. Xu, L. M. Iyer, S. Tasumi, M. C. Kerzic, M. F. Flajnik, L. Aravind, Z. Pancer, and R. A. Mariuzza (2010)
PNAS 107, 13408-13413
   Abstract »    Full Text »    PDF »
V{gamma}2V{delta}2 T Cell Receptor Recognition of Prenyl Pyrophosphates Is Dependent on All CDRs.
H. Wang, Z. Fang, and C. T. Morita (2010)
J. Immunol. 184, 6209-6222
   Abstract »    Full Text »    PDF »
Human cytomegalovirus elicits fetal {gamma}{delta} T cell responses in utero.
D. Vermijlen, M. Brouwer, C. Donner, C. Liesnard, M. Tackoen, M. Van Rysselberge, N. Twite, M. Goldman, A. Marchant, and F. Willems (2010)
J. Exp. Med. 207, 807-821
   Abstract »    Full Text »    PDF »
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 »
{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 »
Photoaffinity Antigens for Human {gamma}{delta} T Cells.
G. Sarikonda, H. Wang, K.-J. Puan, X.-h. Liu, H. K. Lee, Y. Song, M. D. Distefano, E. Oldfield, G. D. Prestwich, and C. T. Morita (2008)
J. Immunol. 181, 7738-7750
   Abstract »    Full Text »    PDF »
Identification of Human T Cell Receptor {gamma}{delta}-recognized Epitopes/Proteins via CDR3{delta} Peptide-based Immunobiochemical Strategy.
H. Chen, X. He, Z. Wang, D. Wu, H. Zhang, C. Xu, H. He, L. Cui, D. Ba, and W. He (2008)
J. Biol. Chem. 283, 12528-12537
   Abstract »    Full Text »    PDF »
Bovine Luteal Cells Stimulate Proliferation of Major Histocompatibility Nonrestricted Gamma Delta T Cells.
T. L Davis and J. L Pate (2007)
Biol Reprod 77, 914-922
   Abstract »    Full Text »    PDF »
Mutations Designed to Destabilize the Receptor-Bound Conformation Increase MICA-NKG2D Association Rate and Affinity.
C. S. E. Lengyel, L. J. Willis, P. Mann, D. Baker, T. Kortemme, R. K. Strong, and B. J. McFarland (2007)
J. Biol. Chem. 282, 30658-30666
   Abstract »    Full Text »    PDF »
The Structure of the Macrophage Signal Regulatory Protein {alpha} (SIRP{alpha}) Inhibitory Receptor Reveals a Binding Face Reminiscent of That Used by T Cell Receptors.
D. Hatherley, K. Harlos, D. C. Dunlop, D. I. Stuart, and A. N. Barclay (2007)
J. Biol. Chem. 282, 14567-14575
   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 »
The TCR Cbeta FG Loop Regulates {alpha}beta T Cell Development..
M. Touma, H.-C. Chang, T. Sasada, M. Handley, L. K. Clayton, and E. L. Reinherz (2006)
J. Immunol. 176, 6812-6823
   Abstract »    Full Text »    PDF »
Epithelial Cells and Their Neighbors. III. Interactions between intraepithelial lymphocytes and neighboring epithelial cells.
W. L. Havran, J. M. Jameson, and D. A. Witherden (2005)
Am J Physiol Gastrointest Liver Physiol 289, G627-G630
   Abstract »    Full Text »    PDF »
Professional Antigen-Presentation Function by Human {gamma}{delta} T Cells.
M. Brandes, K. Willimann, and B. Moser (2005)
Science 309, 264-268
   Abstract »    Full Text »    PDF »
STRUCTURAL BIOLOGY: "D" Is Not for Diversity.
D. N. Garboczi (2005)
Science 308, 209-210
   Abstract »    Full Text »    PDF »
Antigen Recognition Determinants of {gamma}{delta} T Cell Receptors.
S. Shin, R. El-Diwany, S. Schaffert, E. J. Adams, K. C. Garcia, P. Pereira, and Y.-h. Chien (2005)
Science 308, 252-255
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882