PDBsum entry 4jqx

Immune system

PDB id: 4jqx

Contents

Protein chains

276 a.a.

99 a.a.

12 a.a.

Ligands

GOL

ACT ×2

Waters ×201

PDB id:

4jqx

Name:

Immune system

Title:

Hla-b 44:03 In complex with epstein-barr virus bzlf1-derived peptide (residues 169-180)

Structure:

Hla class i histocompatibility antigen, b-44 alpha chain. Chain: a. Fragment: extracellular domains (unp residues 25-302). Synonym: bw-44, mhc class i antigen b 44. Engineered: yes. Beta-2-microglobulin. Chain: c. Fragment: mature protein (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. Human herpesvirus 4.

Resolution:

1.90Å R-factor: 0.197 R-free: 0.231

Authors:

A.Theodossis,A.Welland,S.Gras,J.Rossjohn

Key ref:

M.J.Rist et al. (2013). HLA peptide length preferences control CD8+ T cell responses. J Immunol, 191, 561-571. PubMed id: 23749632 DOI: 10.4049/jimmunol.1300292

Date:

20-Mar-13 Release date: 26-Jun-13

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: 99 a.a.

Protein chain

Q3KSS8  (BZLF1_EBVG) -  Lytic switch protein BZLF1 from Epstein-Barr virus (strain GD1)

Seq: 245 a.a.

Struc: 12 a.a.

* PDB and UniProt seqs differ at 31 residue positions (black crosses)

DOI no: 10.4049/jimmunol.1300292

J Immunol 191:561-571 (2013)

PubMed id: 23749632

HLA peptide length preferences control CD8+ T cell responses.

M.J.Rist, A.Theodossis, N.P.Croft, M.A.Neller, A.Welland, Z.Chen, L.C.Sullivan, J.M.Burrows, J.J.Miles, R.M.Brennan, S.Gras, R.Khanna, A.G.Brooks, J.McCluskey, A.W.Purcell, J.Rossjohn, S.R.Burrows.

ABSTRACT

Class I HLAs generally present peptides of 8-10 aa in length, although it is unclear whether peptide length preferences are affected by HLA polymorphism. In this study, we investigated the CD8(+) T cell response to the BZLF1 Ag of EBV, which includes overlapping sequences of different size that nevertheless conform to the binding motif of the large and abundant HLA-B*44 supertype. Whereas HLA-B*18:01(+) individuals responded strongly and exclusively to the octamer peptide (173)SELEIKRY(180), HLA-B*44:03(+) individuals responded to the atypically large dodecamer peptide (169)EECDSELEIKRY(180), which encompasses the octamer peptide. Moreover, the octamer peptide bound more stably to HLA-B*18:01 than did the dodecamer peptide, whereas, conversely, HLA-B*44:03 bound only the longer peptide. Furthermore, crystal structures of these viral peptide-HLA complexes showed that the Ag-binding cleft of HLA-B*18:01 was more ideally suited to bind shorter peptides, whereas HLA-B*44:03 exhibited characteristics that favored the presentation of longer peptides. Mass spectrometric identification of > 1000 naturally presented ligands revealed that HLA-B*18:01 was more biased toward presenting shorter peptides than was HLA-B*44:03. Collectively, these data highlight a mechanism through which polymorphism within an HLA class I supertype can diversify determinant selection and immune responses by varying peptide length preferences.