HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Kjer-Nielsen, L. Articles by Rossjohn, J. Search for Related Content PubMed PubMed Citation Articles by Kjer-Nielsen, L. Articles by Rossjohn, J.

The Structure of HLA-B8 Complexed to an Immunodominant Viral Determinant: Peptide-Induced Conformational Changes and a Mode of MHC Class I Dimerization¹

Lars Kjer-Nielsen^2,*, Craig S. Clements^2,, Andrew G. Brooks^*, Anthony W. Purcell^*, Marcos R. Fontes^3,, James McCluskey^4,* and Jamie Rossjohn^4,

^* Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria, Australia; Protein Crystallography Unit, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria, Australia; and Protein Crystallography Unit, St. Vincent’s Institute of Medical Research, 41 Victoria Parade, Fitzroy, Victoria, Australia

EBV is a ubiquitous human pathogen that chronically infects up to 90% of the population. Persistent viral infection is characterized by latency and periods of viral replication that are kept in check by a strong antiviral CTL response. Despite the size of the EBV genome, CTL immunity focuses on only a few viral determinants but expands a large primary and memory response toward these epitopes. In unrelated HLA-B8⁺ individuals, the response to the immunodominant latent Ag FLRGRAYGL from Epstein Barr nuclear Ag 3A is largely comprised of CTL clones with identical conserved TCR structures. To better understand the structural correlates of Ag immunodominance and TCR selection bias, we have solved the crystal structure of the HLA-B8-FLRGRAYGL peptide complex to a resolution of 1.9 Å. The structure confirms the importance of P3-Arg, P5-Arg, and P9-Leu as dominant anchor residues involved in peptide binding to HLA-B8. A bulged conformation of the bound peptide provides a structural basis for the critical role of the P7-Tyr residue in T cell recognition. The peptide also induces backbone and side-chain conformational changes in HLA-B8 that are transmitted along the peptide-binding groove in a domino effect. The HLA-B8-FLRGRAYGL complex crystallizes as a dimer in the asymmetric unit and is oriented such that both peptide ligands are projected in the same plane suggesting a higher order arrangement of MHC-peptide complexes that could be involved in formation of the class I Ag-loading complex or in T cell activation.

This article has been cited by other articles:

				E. Spierings, S. Gras, J.-B. Reiser, B. Mommaas, M. Almekinders, M. G. D. Kester, A. Chouquet, M. Le Gorrec, J. W. Drijfhout, F. Ossendorp, et al. Steric Hindrance and Fast Dissociation Explain the Lack of Immunogenicity of the Minor Histocompatibility HA-1Arg Null Allele J. Immunol., April 15, 2009; 182(8): 4809 - 4816. [Abstract] [Full Text] [PDF]

				J. K. Archbold, W. A. Macdonald, S. Gras, L. K. Ely, J. J. Miles, M. J. Bell, R. M. Brennan, T. Beddoe, M. C.J. Wilce, C. S. Clements, et al. Natural micropolymorphism in human leukocyte antigens provides a basis for genetic control of antigen recognition J. Exp. Med., January 16, 2009; 206(1): 209 - 219. [Abstract] [Full Text] [PDF]

				V. Venturi, H. Y. Chin, T. E. Asher, K. Ladell, P. Scheinberg, E. Bornstein, D. van Bockel, A. D. Kelleher, D. C. Douek, D. A. Price, et al. TCR {beta}-Chain Sharing in Human CD8+ T Cell Responses to Cytomegalovirus and EBV J. Immunol., December 1, 2008; 181(11): 7853 - 7862. [Abstract] [Full Text] [PDF]

				V. Venturi, H. Y. Chin, D. A. Price, D. C. Douek, and M. P. Davenport The Role of Production Frequency in the Sharing of Simian Immunodeficiency Virus-Specific CD8+ TCRs between Macaques J. Immunol., August 15, 2008; 181(4): 2597 - 2609. [Abstract] [Full Text] [PDF]

				V. Venturi, K. Kedzierska, D. A. Price, P. C. Doherty, D. C. Douek, S. J. Turner, and M. P. Davenport Sharing of T cell receptors in antigen-specific responses is driven by convergent recombination PNAS, December 5, 2006; 103(49): 18691 - 18696. [Abstract] [Full Text] [PDF]

				J. Racape, F. Connan, J. Hoebeke, J. Choppin, and J.-G. Guillet Influence of dominant HIV-1 epitopes on HLA-A3/peptide complex formation PNAS, November 28, 2006; 103(48): 18208 - 18213. [Abstract] [Full Text] [PDF]

				J. K. Archbold, W. A. Macdonald, J. J. Miles, R. M. Brennan, L. Kjer-Nielsen, J. McCluskey, S. R. Burrows, and J. Rossjohn Alloreactivity between Disparate Cognate and Allogeneic pMHC-I Complexes Is the Result of Highly Focused, Peptide-dependent Structural Mimicry J. Biol. Chem., November 10, 2006; 281(45): 34324 - 34332. [Abstract] [Full Text] [PDF]

				L. K. Ely, T. Beddoe, C. S. Clements, J. M. Matthews, A. W. Purcell, L. Kjer-Nielsen, J. McCluskey, and J. Rossjohn Disparate thermodynamics governing T cell receptor-MHC-I interactions implicate extrinsic factors in guiding MHC restriction PNAS, April 25, 2006; 103(17): 6641 - 6646. [Abstract] [Full Text] [PDF]

				C. Thilo, P. Berglund, S. E. Applequist, J. W. Yewdell, H.-G. Ljunggren, and A. Achour Dissection of the Interaction of the Human Cytomegalovirus-derived US2 Protein with Major Histocompatibility Complex Class I Molecules: PROMINENT ROLE OF A SINGLE ARGININE RESIDUE IN HUMAN LEUKOCYTE ANTIGEN-A2 J. Biol. Chem., March 31, 2006; 281(13): 8950 - 8957. [Abstract] [Full Text] [PDF]

				M. Cebecauer, P. Guillaume, S. Mark, O. Michielin, N. Boucheron, M. Bezard, B. H. Meyer, J.-M. Segura, H. Vogel, and I. F. Luescher CD8+ Cytotoxic T Lymphocyte Activation by Soluble Major Histocompatibility Complex-Peptide Dimers J. Biol. Chem., June 24, 2005; 280(25): 23820 - 23828. [Abstract] [Full Text] [PDF]

				L. K. Ely, K. J. Green, T. Beddoe, C. S. Clements, J. J. Miles, S. P. Bottomley, D. Zernich, L. Kjer-Nielsen, A. W. Purcell, J. McCluskey, et al. Antagonism of Antiviral and Allogeneic Activity of a Human Public CTL Clonotype by a Single Altered Peptide Ligand: Implications for Allograft Rejection J. Immunol., May 1, 2005; 174(9): 5593 - 5601. [Abstract] [Full Text] [PDF]

				C. S. Clements, L. Kjer-Nielsen, L. Kostenko, H. L. Hoare, M. A. Dunstone, E. Moses, K. Freed, A. G. Brooks, J. Rossjohn, and J. McCluskey Crystal structure of HLA-G: A nonclassical MHC class I molecule expressed at the fetal-maternal interface PNAS, March 1, 2005; 102(9): 3360 - 3365. [Abstract] [Full Text] [PDF]

				A. I. Webb, N. A. Borg, M. A. Dunstone, L. Kjer-Nielsen, T. Beddoe, J. McCluskey, F. R. Carbone, S. P. Bottomley, M.-I. Aguilar, A. W. Purcell, et al. The Structure of H-2Kb and Kbm8 Complexed to a Herpes Simplex Virus Determinant: Evidence for a Conformational Switch That Governs T Cell Repertoire Selection and Viral Resistance J. Immunol., July 1, 2004; 173(1): 402 - 409. [Abstract] [Full Text] [PDF]

				A. I. Webb, M. A. Dunstone, W. Chen, M.-I. Aguilar, Q. Chen, H. Jackson, L. Chang, L. Kjer-Nielsen, T. Beddoe, J. McCluskey, et al. Functional and Structural Characteristics of NY-ESO-1-related HLA A2-restricted Epitopes and the Design of a Novel Immunogenic Analogue J. Biol. Chem., May 28, 2004; 279(22): 23438 - 23446. [Abstract] [Full Text] [PDF]

				L. Li and M. Bouvier Structures of HLA-A*1101 Complexed with Immunodominant Nonamer and Decamer HIV-1 Epitopes Clearly Reveal the Presence of a Middle, Secondary Anchor Residue J. Immunol., May 15, 2004; 172(10): 6175 - 6184. [Abstract] [Full Text] [PDF]