3BWA

Crystal Structure of HLA B*3508 in complex with a HCMV 8-mer peptide from the pp65 protein

Summary for 3BWA

• Entry DOI: 10.2210/pdb3bwa/pdb
• Related: 3BW9
• Descriptor: HLA class I histocompatibility antigen, B-35 alpha chain, Beta-2-microglobulin, FPT peptide from 65 kDa lower matrix phosphoprotein, ... (4 entities in total)
• Functional Keywords: hla b*3508, hcmv, pp65, immunology, glycoprotein, host-virus interaction, immune response, membrane, mhc i, polymorphism, transmembrane, ubl conjugation, disease mutation, glycation, immunoglobulin domain, pyrrolidone carboxylic acid, secreted, phosphoprotein, tegument protein, viral matrix protein, virion, 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; Virion tegument : P06725
• Total number of polymer chains: 3
• Total formula weight: 44754.68

Authors

Wynn, K.K.,Marland, Z.,Cooper, L.,Silins, S.L.,Gras, S.,Archbold, J.K.,Tynan, F.E.,Miles, J.J.,McCluskey, J.,Burrows, S.R.,Rossjohn, J.,Khanna, R. (deposition date: 2008-01-08, release date: 2008-04-22, Last modification date: 2024-10-16)

Primary citation

Wynn, K.K.,Fulton, Z.,Cooper, L.,Silins, S.L.,Gras, S.,Archbold, J.K.,Tynan, F.E.,Miles, J.J.,McCluskey, J.,Burrows, S.R.,Rossjohn, J.,Khanna, R.
Impact of clonal competition for peptide-MHC complexes on the CD8+ T-cell repertoire selection in a persistent viral infection
Blood, 111:4283-4292, 2008

PubMed Abstract: CD8(+) T-cell responses to persistent viral infections are characterized by the accumulation of an oligoclonal T-cell repertoire and a reduction in the naive T-cell pool. However, the precise mechanism for this phenomenon remains elusive. Here we show that human cytomegalovirus (HCMV)-specific CD8(+) T cells recognizing distinct epitopes from the pp65 protein and restricted through an identical HLA class I allele (HLA B*3508) exhibited either a highly conserved public T-cell repertoire or a private, diverse T-cell response, which was uniquely altered in each donor following in vitro antigen exposure. Selection of a public T-cell receptor (TCR) was coincident with an atypical major histocompatibility complex (MHC)-peptide structure, in that the epitope adopted a helical conformation that bulged from the peptide-binding groove, while a diverse TCR profile was observed in response to the epitope that formed a flatter, more "featureless" landscape. Clonotypes with biased TCR usage demonstrated more efficient recognition of virus-infected cells, a greater CD8 dependency, and were more terminally differentiated in their phenotype when compared with the T cells expressing diverse TCR. These findings provide new insights into our understanding on how the biology of antigen presentation in addition to the structural features of the pMHC-I might shape the T-cell repertoire and its phenotype.

PubMed: 18270323
DOI: 10.1182/blood-2007-11-122622

Experimental method

X-RAY DIFFRACTION (1.3 Å)