5KD7

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)

Summary for 5KD7

• Entry DOI: 10.2210/pdb5kd7/pdb
• Related: 5KD4
• Descriptor: H-2 class I histocompatibility antigen, D-D alpha chain, Beta-2-microglobulin, Peptide (PV9) of HIV gp120 MN isolate (IGPGRAFYV), ... (6 entities in total)
• Functional Keywords: major histompatibility complex class i, mhc-i, h2-dd, h-2dd, hiv peptide, pvi10, pv9, glycoprotein, immune response, immune system
• Biological source: Mus musculus (Mouse); More
• Total number of polymer chains: 12
• Total formula weight: 179727.78

Authors

Jiang, J.,Natarajan, K.,Margulies, D. (deposition date: 2016-06-07, release date: 2017-10-11, Last modification date: 2023-09-27)

Primary citation

Frey, B.F.,Jiang, J.,Sui, Y.,Boyd, L.F.,Yu, B.,Tatsuno, G.,Billeskov, R.,Solaymani-Mohammadi, S.,Berman, P.W.,Margulies, D.H.,Berzofsky, J.A.
Effects of Cross-Presentation, Antigen Processing, and Peptide Binding in HIV Evasion of T Cell Immunity.
J. Immunol., 200:1853-1864, 2018

PubMed 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 gp120 by mutating a key CatS cleavage site (ThrThr) in the V3 loop of the immunodominant epitope IGPGRAFY to IGPGRAFY to 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.

PubMed: 29374075
DOI: 10.4049/jimmunol.1701523

Experimental method

X-RAY DIFFRACTION (2.35 Å)