PDBsum entry 4qrs

Immune system

PDB id: 4qrs

Contents

Protein chains

276 a.a.

100 a.a.

Ligands

GLU-LEU-LYS-ARG-LYS-MET-ILE-TYR-MET

ACT ×2

Waters ×553

PDB id:

4qrs

Name:

Immune system

Title:

Crystal structure of hla b 0801 In complex with elk_iym, elkrkmiym

Structure:

Hla class i histocompatibility antigen, b-8 alpha chain. Chain: a. Synonym: mhc class i antigen b 8. Engineered: yes. Beta-2-microglobulin. Chain: b. Synonym: beta-2-microglobulin form pi 5.3. Engineered: yes. Major immediate-early protein.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-b, hlab. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: b2m, cdabp0092, hdcma22p. Synthetic: yes. Human herpesvirus 5.

Resolution:

1.40Å R-factor: 0.194 R-free: 0.216

Authors:

S.Gras,K.-A.Twist,J.Rossjohn

Key ref:

C.Smith et al. (2014). Molecular imprint of exposure to naturally occurring genetic variants of human cytomegalovirus on the T cell repertoire. Sci Rep, 4, 3993. PubMed id: 24509977 DOI: 10.1038/srep03993

Date:

02-Jul-14 Release date: 10-Dec-14

Protein chain

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

Seq: 362 a.a.

Struc: 276 a.a.*

Protein chain

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

Seq: 119 a.a.

Struc: 100 a.a.*

* PDB and UniProt seqs differ at 14 residue positions (black crosses)

DOI no: 10.1038/srep03993

Sci Rep 4:3993 (2014)

PubMed id: 24509977

Molecular imprint of exposure to naturally occurring genetic variants of human cytomegalovirus on the T cell repertoire.

C.Smith, S.Gras, R.M.Brennan, N.L.Bird, S.A.Valkenburg, K.A.Twist, J.M.Burrows, J.J.Miles, D.Chambers, S.Bell, S.Campbell, K.Kedzierska, S.R.Burrows, J.Rossjohn, R.Khanna.

ABSTRACT

Exposure to naturally occurring variants of herpesviruses in clinical settings can have a dramatic impact on anti-viral immunity. Here we have evaluated the molecular imprint of variant peptide-MHC complexes on the T-cell repertoire during human cytomegalovirus (CMV) infection and demonstrate that primary co-infection with genetic variants of CMV was coincident with development of strain-specific T-cell immunity followed by emergence of cross-reactive virus-specific T-cells. Cross-reactive CMV-specific T cells exhibited a highly conserved public T cell repertoire, while T cells directed towards specific genetic variants displayed oligoclonal repertoires, unique to each individual. T cell recognition foot-print and pMHC-I structural analyses revealed that the cross-reactive T cells accommodate alterations in the pMHC complex with a broader foot-print focussing on the core of the peptide epitope. These findings provide novel molecular insight into how infection with naturally occurring genetic variants of persistent human herpesviruses imprints on the evolution of the anti-viral T-cell repertoire.