4PR5

Crystal structure of a HLA-B*35:01-HPVG-D5

Summary for 4PR5

• Entry DOI: 10.2210/pdb4pr5/pdb
• Related: 2FYY 3VM7 4PRA 4PRB 4PRD 4PRE 4PRH 4PRI 4PRN 4PRP
• Descriptor: HLA class I histocompatibility antigen, B-35 alpha chain, Beta-2-microglobulin, Epstein-Barr nuclear antigen 1, ... (4 entities in total)
• Functional Keywords: human leukocyte antigen class i, epstein-barr virus, viral escape, t cell receptor, viral immunity, structural biology, immune system
• Biological source: Homo sapiens (human); More
• Cellular location: Membrane; Single-pass type I membrane protein: P30685; Secreted . Note=(Microbial infection) In the presence of M: P61769; Host nucleus : Q3KSS4
• Total number of polymer chains: 3
• Total formula weight: 45001.75

Authors

Yu Chih, L.,Rossjohn, J.,Gras, S. (deposition date: 2014-03-05, release date: 2014-04-16, Last modification date: 2023-09-20)

Primary citation

Liu, Y.C.,Chen, Z.,Neller, M.A.,Miles, J.J.,Purcell, A.W.,McCluskey, J.,Burrows, S.R.,Rossjohn, J.,Gras, S.
A Molecular Basis for the Interplay between T Cells, Viral Mutants, and Human Leukocyte Antigen Micropolymorphism.
J.Biol.Chem., 289:16688-16698, 2014

PubMed Abstract: Mutations within T cell epitopes represent a common mechanism of viral escape from the host protective immune response. The diverse T cell repertoire and the extensive human leukocyte antigen (HLA) polymorphism across populations is the evolutionary response to viral mutation. However, the molecular basis underpinning the interplay between HLA polymorphism, the T cell repertoire, and viral escape is unclear. Here we investigate the T cell response to a HLA-B*35:01- and HLA-B*35:08-restricted (407)HPVGEADYFEY(417) epitope from Epstein-Barr virus and naturally occurring variants at positions 4 and 5 thereof. Each viral variant differently impacted on the epitope's flexibility and conformation when bound to HLA-B*35:08 or HLA-B*35:01. We provide a molecular basis for understanding how the single residue polymorphism that discriminates between HLA-B*35:01/08 profoundly impacts on T cell receptor recognition. Surprisingly, one viral variant (P5-Glu to P5-Asp) effectively changed restriction preference from HLA-B*35:01 to HLA-B*35:08. Collectively, our study portrays the interplay between the T cell response, viral escape, and HLA polymorphism, whereby HLA polymorphism enables altered presentation of epitopes from different strains of Epstein-Barr virus.

PubMed: 24759101
DOI: 10.1074/jbc.M114.563502

Experimental method

X-RAY DIFFRACTION (1.8 Å)