Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 371K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Hennecke, J. Articles by Wiley, D. C. Search for Related Content PubMed PubMed Citation Articles by Hennecke, J. Articles by Wiley, D. C. Social Bookmarking                      What's this?

Original Article

Structure of a Complex of the Human /ß T Cell Receptor (TCR) HA1.7, Influenza Hemagglutinin Peptide, and Major Histocompatibility Complex Class II Molecule, HLA-DR4 (DRA^*0101 and DRB1^,*0401)

Jens Hennecke¹ and Don C. Wiley^1,2

¹ Department of Molecular and Cellular Biology, Harvard University
² Howard Hughes Medical Institute, Cambridge, MA 02138

Address correspondence to Jens Hennecke, Micromet AG, Am Klopferspitz 19, D-82152 Martinsried, Germany. Phone: 49-89-895-277-93; Fax: 49-89-895-277-22; E-mail: jens.hennecke{at}Micromet.de

The /ß T cell receptor (TCR) HA1.7 specific for the hemagglutinin (HA) antigen peptide from influenza A virus is HLA-DR1 restricted but cross-reactive for the HA peptide presented by the allo-major histocompatibility complex (MHC) class II molecule HLA-DR4. We report here the structure of the HA1.7/DR4/HA complex, determined by X-ray crystallography at a resolution of 2.4 Å. The overall structure of this complex is very similar to the previously reported structure of the HA1.7/DR1/HA complex. Amino acid sequence differences between DR1 and DR4, which are located deep in the peptide binding groove and out of reach for direct contact by the TCR, are able to indirectly influence the antigenicity of the pMHC surface by changing the conformation of HA peptide residues at position P5 and P6. Although TCR HA1.7 is cross-reactive for HA presented by DR1 and DR4 and tolerates these conformational differences, other HA-specific TCRs are sensitive to these changes. We also find a dependence of the width of the MHC class II peptide-binding groove on the sequence of the bound peptide by comparing the HA1.7/DR4/HA complex with the structure of DR4 presenting a collagen peptide. This structural study of TCR cross-reactivity emphasizes how MHC sequence differences can affect TCR binding indirectly by moving peptide atoms.

Key Words: T cell receptor • MHC class II • cross-reactivity • antigen recognition • X-ray crystallography

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• MATSUEDA, S., GAO, H., EFFERSON, C. L., TSUDA, N., ISHIYAMA, S., LI, Y., IOANNIDES, M. G., FISK, B., PEOPLES, G. E., IOANNIDES, C. G. (2009). N-Terminally LRMK-linked HER-2 peptides, AE-37 [p776(774-788)] and AE-47 [Ava-F7(776-788)], Aid Differentiation of E75-TCR+CD8+ Cells to Perforin-positive Cells. Anticancer Res 29: 2427-2435 [Abstract] [Full Text]  
• LI, Y., MATSUEDA, S., EFFERSON, C. L., TSUDA, N., KAWANO, K., GAO, H., PEOPLES, G. E., IOANNIDES, C. G. (2009). Distinct Patient Responses to Activation of T-cells by Free HER-2, G89 (777-789) and Protected LRMK-linked HER-2, {AE-39 [p776 (Ava-774-788)], AE-47 [(Ava-776-788)] and AE-37[p776 (774-788)]} Peptides Could Lead to Development of Personalized Cancer Vaccines. Anticancer Res 29: 41-58 [Abstract] [Full Text]  
• Menconi, F., Monti, M. C., Greenberg, D. A., Oashi, T., Osman, R., Davies, T. F., Ban, Y., Jacobson, E. M., Concepcion, E. S., Li, C. W., Tomer, Y. (2008). Molecular amino acid signatures in the MHC class II peptide-binding pocket predispose to autoimmune thyroiditis in humans and in mice. Proc. Natl. Acad. Sci. USA 105: 14034-14039 [Abstract] [Full Text]  
• Kudela, P., Janjic, B., Fourcade, J., Castelli, F., Andrade, P., Kirkwood, J. M., El-Hefnawy, T., Amicosante, M., Maillere, B., Zarour, H. M. (2007). Cross-Reactive CD4+ T Cells against One Immunodominant Tumor-Derived Epitope in Melanoma Patients. J. Immunol. 179: 7932-7940 [Abstract] [Full Text]  
• Parra-Lopez, C., Calvo-Calle, J. M., Cameron, T. O., Vargas, L. E., Salazar, L. M., Patarroyo, M. E., Nardin, E., Stern, L. J. (2006). Major Histocompatibility Complex and T Cell Interactions of a Universal T Cell Epitope from Plasmodium falciparum Circumsporozoite Protein. J. Biol. Chem. 281: 14907-14917 [Abstract] [Full Text]  
• Sospedra, M., Muraro, P. A., Stefanova, I., Zhao, Y., Chung, K., Li, Y., Giulianotti, M., Simon, R., Mariuzza, R., Pinilla, C., Martin, R. (2006). Redundancy in Antigen-Presenting Function of the HLA-DR and -DQ Molecules in the Multiple Sclerosis-Associated HLA-DR2 Haplotype. J. Immunol. 176: 1951-1961 [Abstract] [Full Text]  
• Monneaux, F., Hoebeke, J., Sordet, C., Nonn, C., Briand, J.-P., Maillere, B., Sibillia, J., Muller, S. (2005). Selective Modulation of CD4+ T Cells from Lupus Patients by a Promiscuous, Protective Peptide Analog. J. Immunol. 175: 5839-5847 [Abstract] [Full Text]  
• Sandalova, T., Michaelsson, J., Harris, R. A., Odeberg, J., Schneider, G., Karre, K., Achour, A. (2005). A Structural Basis for CD8+ T Cell-dependent Recognition of Non-homologous Peptide Ligands: IMPLICATIONS FOR MOLECULAR MIMICRY IN AUTOREACTIVITY. J. Biol. Chem. 280: 27069-27075 [Abstract] [Full Text]  
• Greer, J M, Pender, M P (2005). The presence of glutamic acid at positions 71 or 74 in pocket 4 of the HLA-DR{beta}1 chain is associated with the clinical course of multiple sclerosis. J. Neurol. Neurosurg. Psychiatry 76: 656-662 [Abstract] [Full Text]  
• Zavala-Ruiz, Z., Strug, I., Walker, B. D., Norris, P. J., Stern, L. J. (2004). A hairpin turn in a class II MHC-bound peptide orients residues outside the binding groove for T cell recognition. Proc. Natl. Acad. Sci. USA 101: 13279-13284 [Abstract] [Full Text]  
• Fridkis-Hareli, M., Reche, P. A., Reinherz, E. L. (2004). Peptide Variants of Viral CTL Epitopes Mediate Positive Selection and Emigration of Ag-Specific Thymocytes In Vivo. J. Immunol. 173: 1140-1150 [Abstract] [Full Text]  
• Anderson, M. W., Gorski, J. (2003). Cutting Edge: TCR Contacts as Anchors: Effects on Affinity and HLA-DM Stability. J. Immunol. 171: 5683-5687 [Abstract] [Full Text]  
• Zavala-Ruiz, Z., Sundberg, E. J., Stone, J. D., DeOliveira, D. B., Chan, I. C., Svendsen, J., Mariuzza, R. A., Stern, L. J. (2003). Exploration of the P6/P7 Region of the Peptide-binding Site of the Human Class II Major Histocompatability Complex Protein HLA-DR1. J. Biol. Chem. 278: 44904-44912 [Abstract] [Full Text]  
• Ressing, M. E., van Leeuwen, D., Verreck, F. A. W., Gomez, R., Heemskerk, B., Toebes, M., Mullen, M. M., Jardetzky, T. S., Longnecker, R., Schilham, M. W., Ottenhoff, T. H. M., Neefjes, J., Schumacher, T. N., Hutt-Fletcher, L. M., Wiertz, E. J. H. J. (2003). Interference with T cell receptor-HLA-DR interactions by Epstein-Barr virus gp42 results in reduced T helper cell recognition. Proc. Natl. Acad. Sci. USA 100: 11583-11588 [Abstract] [Full Text]  
• Biddison, W. E., Turner, R. V., Gagnon, S. J., Lev, A., Cohen, C. J., Reiter, Y. (2003). Tax and M1 Peptide/HLA-A2-Specific Fabs and T Cell Receptors Recognize Nonidentical Structural Features on Peptide/HLA-A2 Complexes. J. Immunol. 171: 3064-3074 [Abstract] [Full Text]  
• Diaz, G., Amicosante, M., Jaraquemada, D., Butler, R. H., Guillen, M. V., Sanchez, M., Nombela, C., Arroyo, J. (2003). Functional analysis of HLA-DP polymorphism: a crucial role for DP{beta} residues 9, 11, 35, 55, 56, 69 and 84-87 in T cell allorecognition and peptide binding. Int Immunol 15: 565-576 [Abstract] [Full Text]  
• Luz, J. G., Huang, M., Garcia, K. C., Rudolph, M. G., Apostolopoulos, V., Teyton, L., Wilson, I. A. (2002). Structural Comparison of Allogeneic and Syngeneic T Cell Receptor-Peptide-Major Histocompatibility Complex Complexes: A Buried Alloreactive Mutation Subtly Alters Peptide Presentation Substantially Increasing V{beta} Interactions. JEM 195: 1175-1186 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS