PDBsum entry 3vcl

Immune system

PDB id: 3vcl

Contents

Protein chains

275 a.a.

99 a.a.

11 a.a.

Ligands

GOL ×8

Metals

_NI ×4

Waters ×458

PDB id:

3vcl

Name:

Immune system

Title:

Crystal structure of hla-b7 with the hcmv pp65 peptide rpherngftvl

Structure:

Hla class i histocompatibility antigen, b-7 alpha chain. Chain: a. Fragment: unp residues 25-299. Synonym: mhc class i antigen b 7. Engineered: yes. Beta-2-microglobulin. Chain: b. Synonym: beta-2-microglobulin form pi 5.3. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-b. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m. Synthetic: yes. Human herpesvirus 5.

Resolution:

1.70Å R-factor: 0.186 R-free: 0.217

Authors:

J.Petersen,J.Rossjohn

Key ref:

R.M.Brennan et al. (2012). The impact of a large and frequent deletion in the human TCR β locus on antiviral immunity. J Immunol, 188, 2742-2748. PubMed id: 22323539

Date:

04-Jan-12 Release date: 21-Nov-12

Protein chain

P01889  (1B07_HUMAN) -  HLA class I histocompatibility antigen, B alpha chain from Homo sapiens

Seq: 362 a.a.

Struc: 275 a.a.

Protein chain

P61769  (B2MG_HUMAN) -  Beta-2-microglobulin from Homo sapiens

Seq: 119 a.a.

Struc: 99 a.a.

Protein chain

Q6SW59  (PP65_HCMVM) -  65 kDa phosphoprotein from Human cytomegalovirus (strain Merlin)

Seq: 561 a.a.

Struc: 11 a.a.

J Immunol 188:2742-2748 (2012)

PubMed id: 22323539

The impact of a large and frequent deletion in the human TCR β locus on antiviral immunity.

R.M.Brennan, J.Petersen, M.A.Neller, J.J.Miles, J.M.Burrows, C.Smith, J.McCluskey, R.Khanna, J.Rossjohn, S.R.Burrows.

ABSTRACT

The TCR plays a critical role in recognizing intracellular pathogens and initiating pathways leading to the destruction of infected cells by the immune system. Although genetic variability is known to greatly impact on the human immune system and the outcome of infection, the influence of sequence variation leading to the inactivation or deletion of TCR gene segments is unknown. To investigate this issue, we examined the CD8(+) T cell response to an HLA-B7-restricted epitope ((265)RPHERNGFTVL(275)) from the pp65 Ag of human CMV that was highly biased and frequently dominated by a public TCR β-chain encoded by the variable gene segment TRBV4-3. Approximately 40% of humans lack T cells expressing TRBV4-3 because of a 21.5-kb insertion/deletion polymorphism, but these individuals remain responsive to this epitope, using a diverse T cell repertoire characterized by private TCR usage. Although most residues within the bulged 11-mer peptide were accessible for TCR contact, the public and private TCRs showed distinct patterns of sensitivity to amino acid substitution at different positions within the peptide, thereby suggesting that the repertoire diversity generated in the absence of the dominant public TRBV4-3(+) TCR could lead to better protection from viral escape mutation. Thus, variation in the size of the TRBV repertoire clearly contributes toward interindividual variability in immune responses and is presumably maintained in many ethnic groups to enhance the diversity of Ag-specific T cell responses.