PDBsum entry 5kd7

Immune system

PDB id: 5kd7

Contents

Protein chains

273 a.a.

99 a.a.

Ligands

ILE-GLY-PRO-GLY-ARG-ALA-PHE-TYR-VAL ×4

EDO ×7

GOL ×2

Waters ×220

PDB id:

5kd7

Name:

Immune system

Title:

Crystal structure of murine mhc-i h-2dd in complex with murine beta2- microglobulin and a variant of peptide (pv9) of HIV gp120 mn isolate (igpgrafyv)

Structure:

H-2 class i histocompatibility antigen, d-d alpha chain. Chain: a, c, f, i. Synonym: h-2d(d). Engineered: yes. Beta-2-microglobulin. Chain: b, d, g, j. Engineered: yes. Peptide (pv9) of HIV gp120 mn isolate (igpgrafyv). Chain: p, e, h, k.

Source:

Mus musculus. Mouse. Organism_taxid: 10090. Gene: h2-d1. Expressed in: escherichia coli. Expression_system_taxid: 469008. Gene: b2m. Human immunodeficiency virus type 1 group m subtype b (isolate mn).

Resolution:

2.35Å R-factor: 0.199 R-free: 0.249

Authors:

J.Jiang,K.Natarajan,D.Margulies

Key ref:

B.F.Frey et al. (2018). Effects of Cross-Presentation, Antigen Processing, and Peptide Binding in HIV Evasion of T Cell Immunity. J Immunol, 200, 1853-1864. PubMed id: 29374075 DOI: 10.4049/jimmunol.1701523

Date:

07-Jun-16 Release date: 11-Oct-17

Protein chains

P01900  (HA12_MOUSE) -  H-2 class I histocompatibility antigen, D-D alpha chain from Mus musculus

Seq: 365 a.a.

Struc: 273 a.a.

Protein chains

P01887  (B2MG_MOUSE) -  Beta-2-microglobulin from Mus musculus

Seq: 119 a.a.

Struc: 99 a.a.

DOI no: 10.4049/jimmunol.1701523

J Immunol 200:1853-1864 (2018)

PubMed id: 29374075

Effects of Cross-Presentation, Antigen Processing, and Peptide Binding in HIV Evasion of T Cell Immunity.

B.F.Frey, J.Jiang, Y.Sui, L.F.Boyd, B.Yu, G.Tatsuno, R.Billeskov, S.Solaymani-Mohammadi, P.W.Berman, D.H.Margulies, J.A.Berzofsky.

ABSTRACT

Unlike cytosolic processing and presentation of viral Ags by virus-infected cells, Ags first expressed in infected nonprofessional APCs, such as CD4⁺T cells in the case of HIV, are taken up by dendritic cells and cross-presented. This generally requires entry through the endocytic pathway, where endosomal proteases have first access for processing. Thus, understanding virus escape during cross-presentation requires an understanding of resistance to endosomal proteases, such as cathepsin S (CatS). We have modified HIV-1_MNgp120 by mutating a key CatS cleavage site (Thr³²²Thr³²³) in the V3 loop of the immunodominant epitope IGPGRAFYTTto IGPGRAFYVVto prevent digestion. We found this mutation to facilitate cross-presentation and provide evidence from MHC binding and X-ray crystallographic structural studies that this results from preservation of the epitope rather than an increased epitope affinity for the MHC class I molecule. In contrast, when the protein is expressed by a vaccinia virus in the cytosol, the wild-type protein is immunogenic without this mutation. These proof-of-concept results show that a virus like HIV, infecting predominantly nonprofessional presenting cells, can escape T cell recognition by incorporating a CatS cleavage site that leads to destruction of an immunodominant epitope when the Ag undergoes endosomal cross-presentation.