3bwa

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Template:STRUCTURE 3bwa

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

Overview

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.

About this Structure

3BWA is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Impact of clonal competition for peptide-MHC complexes on the CD8+ T-cell repertoire selection in a persistent viral infection., Wynn KK, Fulton Z, Cooper L, Silins SL, Gras S, Archbold JK, Tynan FE, Miles JJ, McCluskey J, Burrows SR, Rossjohn J, Khanna R, Blood. 2008 Apr 15;111(8):4283-92. Epub 2008 Feb 12. PMID:18270323 Page seeded by OCA on Thu Apr 24 09:49:44 2008