PDBsum entry 4xxc

Immune system

PDB id: 4xxc

Contents

Protein chains

276 a.a.

100 a.a.

Ligands

ASP-GLU-LEU-GLU-ILE-LYS-ALA-TYR

ACT

Waters ×514

PDB id:

4xxc

Name:

Immune system

Title:

Hla-b 1801 In complex with a self-peptide, deleikay

Structure:

Hla class i histocompatibility antigen, b-18 alpha chain. Chain: a. Fragment: unp residues 25-303. Synonym: mhc class i antigen b 18. Engineered: yes. Beta-2-microglobulin. Chain: c. Fragment: unp residues 21-119. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hla-b, hlab. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: b2m, cdabp0092, hdcma22p. Synthetic: yes. Organism_taxid: 9606

Resolution:

1.43Å R-factor: 0.206 R-free: 0.235

Authors:

K.M.Hibbert,J.Rossjohn,S.Gras

Key ref:

M.J.Rist et al. (2015). T Cell Cross-Reactivity between a Highly Immunogenic EBV Epitope and a Self-Peptide Naturally Presented by HLA-B*18:01+ Cells. J Immunol, 194, 4668-4675. PubMed id: 25855358 DOI: 10.4049/jimmunol.1500233

Date:

30-Jan-15 Release date: 08-Apr-15

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 19 residue positions (black crosses)

DOI no: 10.4049/jimmunol.1500233

J Immunol 194:4668-4675 (2015)

PubMed id: 25855358

T Cell Cross-Reactivity between a Highly Immunogenic EBV Epitope and a Self-Peptide Naturally Presented by HLA-B*18:01+ Cells.

M.J.Rist, K.M.Hibbert, N.P.Croft, C.Smith, M.A.Neller, J.M.Burrows, J.J.Miles, A.W.Purcell, J.Rossjohn, S.Gras, S.R.Burrows.

ABSTRACT

T cell cross-reactivity underpins the molecular mimicry hypothesis in which microbial peptides sharing structural features with host peptides stimulate T cells that cross-react with self-peptides, thereby initiating and/or perpetuating autoimmune disease. EBV represents a potentially important factor in the pathogenesis of several T cell-mediated autoimmune disorders, with molecular mimicry a likely mechanism. In this study, we describe a human self-peptide (DELEIKAY) that is a homolog of a highly immunogenic EBV T cell epitope (SELEIKRY) presented by HLA-B*18:01. This self-peptide was shown to bind stably to HLA-B*18:01, and peptide elution/mass spectrometric studies showed it is naturally presented by this HLA molecule on the surface of human cells. A significant proportion of CD8(+) T cells raised from some healthy individuals against this EBV epitope cross-reacted with the self-peptide. A diverse array of TCRs was expressed by the cross-reactive T cells, with variable functional avidity for the self-peptide, including some T cells that appeared to avoid autoreactivity by a narrow margin, with only 10-fold more of the self-peptide required for equivalent activation as compared with the EBV peptide. Structural studies revealed that the self-peptide-HLA-B*18:01 complex is a structural mimic of the EBV peptide-HLA-B*18:01 complex, and that the strong antiviral T cell response is primarily dependent on the alanine/arginine mismatch at position 7. To our knowledge, this is the first report confirming the natural presentation of a self-peptide cross-recognized in the context of self-HLA by EBV-reactive CD8(+) T cells. These results illustrate how aberrant immune responses and immunopathological diseases could be generated by EBV infection.