Home LiteratureArticle Details
PMID: 11060013 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Structure of a covalently stabilized complex of a human alphabeta T-cell receptor, influenza HA peptide and MHC class II molecule, HLA-DR1.

The EMBO journal ·Vol. 19 ·No. 21 ·2000-11-01 ·Pages 5611-24

Hennecke J, Carfi A, Wiley DC

Abstract

An alphabeta T-cell receptor (alphabetaTCR)/hemagglutinin (HA) peptide/human leukocyte antigen (HLA)-DR1 complex was stabilized by flexibly linking the HA peptide with the human HA1.7 alphabetaTCR, to increase the local concentration of the interacting proteins once the peptide has been loaded onto the major histocompatibility complex (MHC) molecule. The structure of the complex, determined by X-ray crystallography, has a binding mode similar to that of the human B7 alphabetaTCR on a pMHCI molecule. Twelve of the 15 MHC residues contacted are at the same positions observed earlier in class I MHC/peptide/TCR complexes. One contact, to an MHC loop outside the peptide-binding site, is conserved and specific to pMHCII complexes. TCR gene usage in the response to HA/HLA-DR appears to conserve charged interactions between three lysines of the peptide and acidic residues on the TCR.

MeSH Terms
Amino Acid Sequence Binding Sites/genetics Crystallography, X-Ray Drug Stability HLA-DR1 Antigen/chemistry,genetics Hemagglutinin Glycoproteins, Influenza Virus/chemistry,genetics Humans In Vitro Techniques Macromolecular Substances Models, Molecular Molecular Sequence Data Protein Conformation Protein Engineering Protein Folding Receptors, Antigen, T-Cell, alpha-beta/chemistry,genetics Recombinant Proteins/chemistry,genetics Sequence Homology, Amino Acid Static Electricity
Chemicals
HLA-DR1 Antigen Hemagglutinin Glycoproteins, Influenza Virus Macromolecular Substances Receptors, Antigen, T-Cell, alpha-beta Recombinant Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hennecke J
Department of Molecular and Cellular Biology, Harvard University, Howard Hughes Medical Institute, 7 Divinity Avenue, Cambridge, MA 02138, USA.
Carfi A
Wiley D C
References (67)
67 references, click to expand
  1. Biased T-cell receptor usage is associated with allelic variation in the MHC class II peptide binding groove.
    Immunogenetics. 1999 Jun;49(6):532-40 PMID: 10380698
  2. Four A6-TCR/peptide/HLA-A2 structures that generate very different T cell signals are nearly identical.
    Immunity. 1999 Jul;11(1):45-56 PMID: 10435578
  3. The crystal structure of a T cell receptor in complex with peptide and MHC class II.
    Science. 1999 Dec 3;286(5446):1913-21 PMID: 10583947
  4. Perspectives: protein structure. Class-conscious TCR?
    Science. 1999 Dec 3;286(5446):1867-8 PMID: 10610577
  5. Determinants of the peptide-induced conformational change in the human class II major histocompatibility complex protein HLA-DR1.
    J Biol Chem. 2000 Jan 21;275(3):2165-73 PMID: 10636922
  6. A functional hot spot for antigen recognition in a superagonist TCR/MHC complex.
    Immunity. 2000 Mar;12(3):251-61 PMID: 10755612
  7. A structural framework for deciphering the link between I-Ag7 and autoimmune diabetes.
    Science. 2000 Apr 21;288(5465):505-11 PMID: 10775108
  8. IMGT/HLA database--a sequence database for the human major histocompatibility complex.
    Tissue Antigens. 2000 Mar;55(3):280-7 PMID: 10777106
  9. Structural, biochemical, and biophysical studies of HLA-A2/altered peptide ligands binding to viral-peptide-specific human T-cell receptors.
    Cold Spring Harb Symp Quant Biol. 1999;64:235-41 PMID: 11232291
  10. Mapping T-cell receptor-peptide contacts by variant peptide immunization of single-chain transgenics.
    Nature. 1992 Jan 16;355(6357):224-30 PMID: 1309938
  11. The human class II MHC protein HLA-DR1 assembles as empty alpha beta heterodimers in the absence of antigenic peptide.
    Cell. 1992 Feb 7;68(3):465-77 PMID: 1371238
  12. The somatic generation of immune recognition.
    Eur J Immunol. 1971 Jan;1(1):1-9 PMID: 14978855
  13. Raster3D Version 2.0. A program for photorealistic molecular graphics.
    Acta Crystallogr D Biol Crystallogr. 1994 Nov 1;50(Pt 6):869-73 PMID: 15299354
  14. Major histocompatibility complex independent clonal T cell anergy by direct interaction of Staphylococcus aureus enterotoxin B with the T cell antigen receptor.
    J Exp Med. 1992 Jun 1;175(6):1493-9 PMID: 1588277
  15. Molecular components of T-cell recognition.
    Annu Rev Immunol. 1992;10:835-73 PMID: 1591005
  16. Single amino acid changes in DR and antigen define residues critical for peptide-MHC binding and T cell recognition.
    J Immunol. 1991 Apr 1;146(7):2331-40 PMID: 1706393
  17. On the interaction of promiscuous antigenic peptides with different DR alleles. Identification of common structural motifs.
    J Immunol. 1991 Oct 15;147(8):2663-9 PMID: 1717570
  18. Antigen analog-major histocompatibility complexes act as antagonists of the T cell receptor.
    Cell. 1992 Feb 21;68(4):625-34 PMID: 1739971
  19. Protein folding and association: insights from the interfacial and thermodynamic properties of hydrocarbons.
    Proteins. 1991;11(4):281-96 PMID: 1758883
  20. Improved methods for building protein models in electron density maps and the location of errors in these models.
    Acta Crystallogr A. 1991 Mar 1;47 ( Pt 2):110-9 PMID: 2025413
  21. Peptide binding to HLA-DR1: a peptide with most residues substituted to alanine retains MHC binding.
    EMBO J. 1990 Jun;9(6):1797-803 PMID: 2189723
  22. Use of T7 RNA polymerase to direct expression of cloned genes.
    Methods Enzymol. 1990;185:60-89 PMID: 2199796
  23. pH-induced denaturation of proteins: a single salt bridge contributes 3-5 kcal/mol to the free energy of folding of T4 lysozyme.
    Biochemistry. 1990 Mar 6;29(9):2403-8 PMID: 2337607
  24. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention.
    Cell. 1988 Jul 15;54(2):263-73 PMID: 2455603
  25. Restricted use of T cell receptor V genes in murine autoimmune encephalomyelitis raises possibilities for antibody therapy.
    Cell. 1988 Aug 12;54(4):577-92 PMID: 2456857
  26. [33] AMoRe: An automated molecular replacement program package.
    Methods Enzymol. 1997;276:581-594 PMID: 27799116
  27. Structural model of HLA-DR1 restricted T cell antigen recognition.
    Cell. 1988 Feb 26;52(4):515-23 PMID: 2963699
  28. T-cell antigen receptor genes and T-cell recognition.
    Nature. 1988 Aug 4;334(6181):395-402 PMID: 3043226
  29. The outline structure of the T-cell alpha beta receptor.
    EMBO J. 1988 Dec 1;7(12):3745-55 PMID: 3208747
  30. Antigen-specific human T lymphocyte clones: viral antigen specificity of influenza virus-immune clones.
    J Immunol. 1982 Mar;128(3):1428-32 PMID: 6173437
  31. Human T-cell clones recognize chemically synthesized peptides of influenza haemagglutinin.
    Nature. 1982 Nov 4;300(5887):66-9 PMID: 6982419
  32. Preferential usage of the T-cell receptor by influenza virus hemagglutinin-specific human CD4+ T lymphocytes: in vitro life span of clonotypic T cells.
    J Virol. 1995 Dec;69(12):8046-50 PMID: 7494319
  33. The inhibition of different T cell lines specific for the same antigen with TCR antagonist peptides.
    J Immunol. 1993 Dec 15;151(12):6815-21 PMID: 7505016
  34. Evidence that the antigen receptors of cytotoxic T lymphocytes interact with a common recognition pattern on the H-2Kb molecule.
    Immunity. 1995 Nov;3(5):573-82 PMID: 7584147
  35. Mediation by HLA-DM of dissociation of peptides from HLA-DR.
    Nature. 1995 Jun 29;375(6534):802-6 PMID: 7596415
  36. Mapping T cell recognition: the identification of a T cell receptor residue critical to the specific interaction with an influenza hemagglutinin peptide.
    Eur J Immunol. 1995 Jun;25(6):1654-62 PMID: 7614994
  37. Evidence for multivalent structure of T-cell antigen receptor complex.
    Mol Immunol. 1995 Aug;32(11):829-39 PMID: 7675043
  38. Molecular basis for degenerate T-cell recognition of one peptide in the context of several DR molecules.
    Hum Immunol. 1994 Sep;41(1):28-33 PMID: 7836061
  39. Three-dimensional structure of a peptide extending from one end of a class I MHC binding site.
    Nature. 1994 Oct 13;371(6498):626-9 PMID: 7935798
  40. Antigenic peptide binding by class I and class II histocompatibility proteins.
    Structure. 1994 Apr 15;2(4):245-51 PMID: 8087551
  41. Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide.
    Nature. 1994 Mar 17;368(6468):215-21 PMID: 8145819
  42. Production of soluble MHC class II proteins with covalently bound single peptides.
    Nature. 1994 May 12;369(6476):151-4 PMID: 8177320
  43. Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1.
    Nature. 1993 Jul 1;364(6432):33-9 PMID: 8316295
  44. Functional consequences of engagement of the T cell receptor by low affinity ligands.
    J Immunol. 1993 Jan 1;150(1):1-7 PMID: 8417115
  45. T cell receptor antagonism mediated by interaction between T cell receptor junctional residues and peptide antigen analogues.
    J Immunol. 1993 May 15;150(10):4277-83 PMID: 8482836
  46. Human T-cell receptor variable gene segment families.
    Immunogenetics. 1995;42(6):455-500 PMID: 8550092
  47. The repertoire of T cells shaped by a single MHC/peptide ligand.
    Cell. 1996 Feb 23;84(4):521-9 PMID: 8598039
  48. The specificity and orientation of a TCR to its peptide-MHC class II ligands.
    Immunity. 1996 Apr;4(4):367-76 PMID: 8612131
  49. Importance of two buried salt bridges in the stability and folding pathway of barnase.
    Biochemistry. 1996 May 28;35(21):6786-94 PMID: 8639630
  50. Modulation of promiscuous T cell receptor recognition by mutagenesis of CDR2 residues.
    J Exp Med. 1996 May 1;183(5):2043-51 PMID: 8642315
  51. The two membrane proximal domains of CD4 interact with the T cell receptor.
    J Exp Med. 1996 May 1;183(5):2097-107 PMID: 8642320
  52. An alphabeta T cell receptor structure at 2.5 A and its orientation in the TCR-MHC complex.
    Science. 1996 Oct 11;274(5285):209-19 PMID: 8824178
  53. Structure of the complex between human T-cell receptor, viral peptide and HLA-A2.
    Nature. 1996 Nov 14;384(6605):134-41 PMID: 8906788
  54. Assembly, specific binding, and crystallization of a human TCR-alphabeta with an antigenic Tax peptide from human T lymphotropic virus type 1 and the class I MHC molecule HLA-A2.
    J Immunol. 1996 Dec 15;157(12):5403-10 PMID: 8955188
  55. T cell receptor recognition of MHC class II-bound peptide flanking residues enhances immunogenicity and results in altered TCR V region usage.
    Immunity. 1997 Sep;7(3):387-99 PMID: 9324359
  56. X-ray crystal structure of HLA-DR4 (DRA*0101, DRB1*0401) complexed with a peptide from human collagen II.
    Immunity. 1997 Oct;7(4):473-81 PMID: 9354468
  57. Alphabeta T cell receptor interactions with syngeneic and allogeneic ligands: affinity measurements and crystallization.
    Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):13838-43 PMID: 9391114
  58. Structural basis of plasticity in T cell receptor recognition of a self peptide-MHC antigen.
    Science. 1998 Feb 20;279(5354):1166-72 PMID: 9469799
  59. Assembly of the TCR/CD3 complex: CD3 epsilon/delta and CD3 epsilon/gamma dimers associate indistinctly with both TCR alpha and TCR beta chains. Evidence for a double TCR heterodimer model.
    Eur J Immunol. 1998 Jan;28(1):12-21 PMID: 9485181
  60. Identification of a common docking topology with substantial variation among different TCR-peptide-MHC complexes.
    Curr Biol. 1998 Mar 26;8(7):409-12 PMID: 9545202
  61. Two human T cell receptors bind in a similar diagonal mode to the HLA-A2/Tax peptide complex using different TCR amino acids.
    Immunity. 1998 Apr;8(4):403-11 PMID: 9586631
  62. Ligand recognition by alpha beta T cell receptors.
    Annu Rev Immunol. 1998;16:523-44 PMID: 9597140
  63. Crystallography & NMR system: A new software suite for macromolecular structure determination.
    Acta Crystallogr D Biol Crystallogr. 1998 Sep 1;54(Pt 5):905-21 PMID: 9757107
  64. The structure of HLA-DM, the peptide exchange catalyst that loads antigen onto class II MHC molecules during antigen presentation.
    Immunity. 1998 Sep;9(3):377-83 PMID: 9768757
  65. Folding, heterodimeric association and specific peptide recognition of a murine alphabeta T-cell receptor expressed in Escherichia coli.
    J Mol Biol. 1999 Jan 29;285(4):1831-43 PMID: 9917415
  66. Profound enhancement of T cell activation mediated by the interaction between the TCR and the D3 domain of CD4.
    J Immunol. 1999 Feb 1;162(3):1431-9 PMID: 9973399
  67. Multivalent structure of an alphabetaT cell receptor.
    Proc Natl Acad Sci U S A. 1999 Feb 16;96(4):1547-52 PMID: 9990061
Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/19.21.5611
Published
2000-11-01
Pages
5611-24
Language
English
Region
England
NLM ID
8208664
PMCID
PMC305780
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/19.21.5611 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2