Crystal Structure of a Complex of a Human alpha/beta-T cell Receptor; Influenza HA Antigen Peptide; and MHC Class II Molecule; HLA-DR4


Tab-View Sample


T-Cell Epitope
Epitope  
   
Complex PDB ID 1J8H
Accession Number 3DIEP0276
IEDB ID 48237
Epitope Sequence PKYVKQNTLKLAT
Starting Position306
Ending Position318
Epitope Type Linear Epitope

Assay Information  
Assay Antigen PKYVKQNTLKLAT Hemagglutinin precursor (322-334) Influenza A virus (A/Aichi/2/1968(H3N2))
PDB CategoryIMMUNE SYSTEM
Keyword protein-protein complex; immunoglobulin fold; IMMUNE SYSTEM
Antibody Residues Interacting with Antigen Open in new window      Download dimplot pdb file
Antibody Chain 1 PDB Chain D
Antigen PDB ChainC
CommentsThis structure is very similar to the structure of the TCR HA1.7/DR1/HA complex [PDB: 1FYT]. Only small conformational differences are observed in the polypeptide mainchain of the HA peptide and the MHC molecule.

Experimental Details
Method
X-RAY DIFFRACTION
Resolution
2.4
R-Value
Space Group
C 1 2 1
Unit Cell
Length(Å) Angle(°)
a = 143.753 α = 90
b = 73.317 β = 108.52
c = 123.033 γ = 90


Source Information  
Structure Determination Method X-RAY DIFFRACTION
Host OrganismDrosophila melanogaster
Host Taxonomic ID 7227

Ligand non-polymer
 
Ligand NameN-ACETYL-D-GLUCOSAMINE
Chem Name NAG
Ligand Name2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE
Chem Name NDG
Ligand NameN-ACETYL-D-GLUCOSAMINE
Chem Name NAG
Ligand Name2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE
Chem Name NDG

Sequence


Protein Name
2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE
Poly type
polypeptide(L)
Sequence status
Complete

Primary Sequence

Entity ID
1
Chain ID
A
Source Method
genetically manipulated
Molecule Name
HLA CLASS II HISTOCOMPATIBILITY ANTIGEN, DR ALPHA CHAIN
Fragment Name
Extracellular Domain
Sequence Length
181

I K E E H V I I Q A E F Y L N P D Q S G E F M F D F D G D E I F H V D M A K K E T V W R L E E F G R F A S F E A Q G A L A N I A V D K A N L E I M T K R S N Y T P I T N V P P E V T V L T N S P V E L R E P N V L I C F I D K F T P P V V N V T W L R N G K P V T T G V S E T V F L P R E D H L F R K F H Y L P F L P S T E D V Y D C R V E H W G L D E P L L K H W E F D
The amino acid color is based upon Bob Fletterick's 'Shapely Models'.(Ref. & Table)
Primary Sequence

Entity ID
2
Chain ID
B
Source Method
genetically manipulated
Molecule Name
HLA CLASS II HISTOCOMPATIBILITY ANTIGEN, DR-4 BETA CHAIN
Fragment Name
Extracellular Domain
Sequence Length
192

G D T R P R F L E Q V K H E C H F F N G T E R V R F L D R Y F Y H Q E E Y V R F D S D V G E Y R A V T E L G R P D A E Y W N S Q K D L L E Q K R A A V D T Y C R H N Y G V G E S F T V Q R R V Y P E V T V Y P A K T Q P L Q H H N L L V C S V N G F Y P G S I E V R W F R N G Q E E K T G V V S T G L I Q N G D W T F Q T L V M L E T V P R S G E V Y T C Q V E H P S V T S P L T V E W R A R S
The amino acid color is based upon Bob Fletterick's 'Shapely Models'.(Ref. & Table)
Primary Sequence

Entity ID
3
Chain ID
C
Source Method
genetically manipulated
Molecule Name
HEMAGGLUTININ HA1 PEPTIDE CHAIN
Fragment Name
Antigen Peptide
Sequence Length
13

P K Y V K Q N T L K L A T
The amino acid color is based upon Bob Fletterick's 'Shapely Models'.(Ref. & Table)
Primary Sequence

Entity ID
4
Chain ID
D
Source Method
genetically manipulated
Molecule Name
T-CELL RECEPTOR ALPHA CHAIN
Fragment Name
Extracellular Domain
Sequence Length
212

Q S V T Q L G S H V S V S E G A L V L L R C N Y S S S V P P Y L F W Y V Q Y P N Q G L Q L L L K Y T S A A T L V K G I N G F E A E F K K S E T S F H L T K P S A H M S D A A E Y F C A V S E S P F G N E K L T F G T G T R L T I I P N I Q N P D P A V Y Q L R D S K S S D K S V C L F T D F D S Q T N V S Q S K D S D V Y I T D K T V L D M R S M D F K S N S A V A W S N K S D F A C A N A F N N S I I P E D T F F P S P E S S C D V K
The amino acid color is based upon Bob Fletterick's 'Shapely Models'.(Ref. & Table)
Primary Sequence

Entity ID
5
Chain ID
E
Source Method
genetically manipulated
Molecule Name
T-CELL RECEPTOR BETA CHAIN
Fragment Name
Extracellular Domain
Sequence Length
246

V K V T Q S S R Y L V K R T G E K V F L E C V Q D M D H E N M F W Y R Q D P G L G L R L I Y F S Y D V K M K E K G D I P E G Y S V S R E K K E R F S L I L E S A S T N Q T S M Y L C A S S S T G L P Y G Y T F G S G T R L T V V E D L N K V F P P E V A V F E P S E A E I S H T Q K A T L V C L A T G F F P D H V E L S W W V N G K E V H S G V S T D P Q P L K E Q P A L N D S R Y S L S S R L R V S A T F W Q N P R N H F R C Q V Q F Y G L S E N D E W T Q D R A K P V T Q I V S A E A W G R A D C G F T
The amino acid color is based upon Bob Fletterick's 'Shapely Models'.(Ref. & Table)

X-RAY DIFFRACTION

Crystalization

pH
7
pH details
13% PEG 8000, 1 M NaCl, 100 mM HEPES, pH 7.0, VAPOR DIFFUSION, SITTING DROP, temperature 291K
temparature
291
temparature Detail


Crystal Data
Unit Cell
Space group
C 1 2 1
Length
Angle
°
a  =
143.753
α  =
90
b  =
73.317
β  =
108.52
c  =
123.033
γ  =
90


Diffraction
Diffraction Detector
Diffraction radiation
Detector
CCD
Monochromator
Type
APS BEAMLINE 14-BM-C
Diffraction Source
Detail
Source
SYNCHROTRON
Collection date
8/11/2000
Type
APS BEAMLINE 14-BM-C


Refinement Data
Reflection Details
Structure Solution Method
MOLECULAR REPLACEMENT
Percent Possible(Observed)
96.8
Resolution(High)
2.4
R-Factor(Observed)
Cut-off Sigma(F)
0
R-Work
0.211
Number Reflections(Observed)
46185
R-Free
No. of Non-Hydrogen atoms
Used in Refinement
Protein atom
6547
Nucleic acid atom
0
Heterogen Atoms
56
Solvent Atoms
305
Total Atoms
6908


Software and Computing
Computing
Software
Data Reduction (intensity integration)
DENZO
model building
Data Reduction (data scaling)
SCALEPACK
refinement
CNS 1.0
Structure Solution
AMORE
Structure Refinement
CNS 1.0

GO functional annotation for 1j8h



Literature reference

Title
Structure of a complex of the human alpha/beta T cell receptor (TCR) HA1.7, influenza hemagglutinin peptide, and major histocompatibility complex class II molecule, HLA-DR4 (DRA*0101 and DRB1*0401): insight into TCR cross-restriction and alloreactivity.
Authors
Journal
Year
Journal Volume
First Page
Last Page
PubMed Abstract
The alpha/beta 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 A. 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.
PubMed ID
Search related article in PubMed
Keywords
protein-protein complex; immunoglobulin fold; IMMUNE SYSTEM




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Ag-Ab Interaction of the1J8H between chain "C" and chain "D"



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Epitope found in chain   :C                                                                                           
Epitope Sequence:- PKYVKQNTLKLAT
Epitope Position found in PDB File   :   306-318  (Highlighted in white spacefill model)
P K Y V K Q N T L K L A T

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Reference :
Herraez, Angel (2006), "Biomolecules in the Computer: Jmol to the Rescue", Biochemistry and Molecular Biology Education 34 (4): 255-261.



Links to external databases and resources



The IEDB contains data related to antibody and T cell epitopes for humans, non-human primates, rodents, and other animal species. Curation of peptidic epitope data relating to all infectious diseases.
Bcipep is collection of the peptides having the role in Humoral immunity. The peptides in the database has varying measure of immunogenicity.This database can assist in the development of method for predicting B cell epitopes, desigining synthetic vaccines and in disease diagnosis.
A DATABASE OF MHC LIGANDS AND PEPTIDE MOTIFS (Ver. 1.0) SYFPEITHI is a database comprising more than 7000 peptide sequences known to bind class I and class II MHC molecules. The entries are compiled from published reports only.
The HIV databases contain data on HIV genetic sequences, immunological epitopes, drug resistance-associated mutations, and vaccine trials. The website also gives access to a large number of tools that can be used to analyze these data. This project is funded by the Division of AIDS of the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH). Click on any of the links below to access a database.
The aim of ABCpred server is to predict B cell epitope(s) in an antigen sequence, using artificial neural network. This is the first server developed based on recurrent neural network (machine based technique) using fixed length patterns.
EPIPREDICT is a new and reliable software to predict HLA-class II restricted T cell epitopes and ligands.
Expasy ProtScale ProtScale [Reference / Documentation] allows you to compute and represent the profile produced by any amino acid scale on a selected protein.
MHCBN is a curated database consisting of detailed information about major histocompatibility complex (MHC) binding, non-binding peptides, and T-cell epitopes. Version 4.0 provides information about peptides interacting with TAP and MHC-linked autoimmune diseases.
AntiJen v2.0 is a database containing quantitative binding data for peptides binding to MHC ligands, TCR-MHC complexes, T cell epitopes, TAP, B cell epitope molecules, and immunological protein-protein interactions. AntiJen includes a peptide library, copy numbers, and diffusion coefficient data. All entries are from published experimentally determined data. The database currently holds over 24,000 entries. No data in AntiJen is from prediction experiments.
HLA Peptide Binding Predictions Function: Rank potential 8-mer, 9-mer, or 10-mer peptides based on a predicted half-time of dissociation to HLA class I molecules. The analysis is based on coefficient tables deduced from the published literature by Dr. Kenneth Parker, Children's Hospital Boston (email: kenneth.parker@childrens.harvard.edu ). Another web site for predicting which peptides bind to MHC molecules is SYFPEITHI, developed by Hans-Georg Rammensee's lab.
AllergenOnline provides access to a peer reviewed allergen list and sequence searchable database intended for identifying proteins that may present a potential risk of allergenic cross-reactivity. This website was designed to help in assessing the safety of proteins that may be introduced into foods through genetic engineering or food processing methods.
The I.U.I.S. Allergen Nomenclature Sub-committee operates under the auspices of the International Union of Immunological Societies (I.U.I.S.) and the World Health Organisation (W.H.O.). The objectives of the I.U.I.S. Allergen Nomenclature Sub-committee are to Maintain a unique and unambiguous nomenclature for allergen molecules and Maintain the ‘official list of allergens’.
Superficial is tool for the identification of potential epitopes or binding sites.
UMAS is a server which provides mirrors of a list of various epitope prediction tools and databases.
MAPPP will predict possible antigenic peptides to be processed and finally presented on cell surfaces. This database aides in the prediction of immunodominant T-cell epitopes and is able to predict the proteasomal cleavage of proteins into smaller fragments, and the binding of peptide sequences to MHC class I molecules.
JenPepM is a database of quantitative binding data for immunological protein-peptide interactions, which allows speedy access to binding data through simple on-line interfaces and effective search mechanisms.
Protall database contains biochemical and clinical information about plant food allergens involved in classical IgE-induced hypersensitivity reactions about 77 allergens from 48 plant species. There are many foods for which a case history of an allergic reaction has been reported for which the allergens responsible have not been described. These are not included in the database.
IMGT®, the international ImMunoGeneTics information system is a high-quality integrated knowledge resource specialized in the immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC), immunoglobulin superfamily (IgSF), major histocompatibility complex superfamily (MhcSF) and related proteins of the immune system (RPI) of human and other vertebrate species.
The IEDB contains data related to antibody and T cell epitopes for humans, non-human primates, rodents, and other animal species. Curation of peptidic epitope data relating to all infectious diseases.
Bcipep is collection of the peptides having the role in Humoral immunity. The peptides in the database has varying measure of immunogenicity.This database can assist in the development of method for predicting B cell epitopes, desigining synthetic vaccines and in disease diagnosis.
A DATABASE OF MHC LIGANDS AND PEPTIDE MOTIFS (Ver. 1.0) SYFPEITHI is a database comprising more than 7000 peptide sequences known to bind class I and class II MHC molecules. The entries are compiled from published reports only.
The HIV databases contain data on HIV genetic sequences, immunological epitopes, drug resistance-associated mutations, and vaccine trials. The website also gives access to a large number of tools that can be used to analyze these data. This project is funded by the Division of AIDS of the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH). Click on any of the links below to access a database.
The aim of ABCpred server is to predict B cell epitope(s) in an antigen sequence, using artificial neural network. This is the first server developed based on recurrent neural network (machine based technique) using fixed length patterns.
EPIPREDICT is a new and reliable software to predict HLA-class II restricted T cell epitopes and ligands.
Expasy ProtScale ProtScale [Reference / Documentation] allows you to compute and represent the profile produced by any amino acid scale on a selected protein.
MHCBN is a curated database consisting of detailed information about major histocompatibility complex (MHC) binding, non-binding peptides, and T-cell epitopes. Version 4.0 provides information about peptides interacting with TAP and MHC-linked autoimmune diseases.
AntiJen v2.0 is a database containing quantitative binding data for peptides binding to MHC ligands, TCR-MHC complexes, T cell epitopes, TAP, B cell epitope molecules, and immunological protein-protein interactions. AntiJen includes a peptide library, copy numbers, and diffusion coefficient data. All entries are from published experimentally determined data. The database currently holds over 24,000 entries. No data in AntiJen is from prediction experiments.
HLA Peptide Binding Predictions Function: Rank potential 8-mer, 9-mer, or 10-mer peptides based on a predicted half-time of dissociation to HLA class I molecules. The analysis is based on coefficient tables deduced from the published literature by Dr. Kenneth Parker, Children's Hospital Boston (email: kenneth.parker@childrens.harvard.edu ). Another web site for predicting which peptides bind to MHC molecules is SYFPEITHI, developed by Hans-Georg Rammensee's lab.
AllergenOnline provides access to a peer reviewed allergen list and sequence searchable database intended for identifying proteins that may present a potential risk of allergenic cross-reactivity. This website was designed to help in assessing the safety of proteins that may be introduced into foods through genetic engineering or food processing methods.
The I.U.I.S. Allergen Nomenclature Sub-committee operates under the auspices of the International Union of Immunological Societies (I.U.I.S.) and the World Health Organisation (W.H.O.). The objectives of the I.U.I.S. Allergen Nomenclature Sub-committee are to Maintain a unique and unambiguous nomenclature for allergen molecules and Maintain the ‘official list of allergens’.
Superficial is tool for the identification of potential epitopes or binding sites.
UMAS is a server which provides mirrors of a list of various epitope prediction tools and databases.
MAPPP will predict possible antigenic peptides to be processed and finally presented on cell surfaces. This database aides in the prediction of immunodominant T-cell epitopes and is able to predict the proteasomal cleavage of proteins into smaller fragments, and the binding of peptide sequences to MHC class I molecules.
JenPepM is a database of quantitative binding data for immunological protein-peptide interactions, which allows speedy access to binding data through simple on-line interfaces and effective search mechanisms.
Protall database contains biochemical and clinical information about plant food allergens involved in classical IgE-induced hypersensitivity reactions about 77 allergens from 48 plant species. There are many foods for which a case history of an allergic reaction has been reported for which the allergens responsible have not been described. These are not included in the database.
IMGT®, the international ImMunoGeneTics information system is a high-quality integrated knowledge resource specialized in the immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC), immunoglobulin superfamily (IgSF), major histocompatibility complex superfamily (MhcSF) and related proteins of the immune system (RPI) of human and other vertebrate species.