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

References listed in PDB file

Key reference

• Title: Effects of cross-Presentation, Antigen processing, And peptide binding in HIV evasion of t cell immunity.
• Authors: 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.
• Ref.: J Immunol, 2018, 200, 1853-1864. [DOI no: 10.4049/jimmunol.1701523]
• PubMed id: 29374075

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.