Wynn, Katherine K., Fulton, Zara, Cooper, Leanne, Silins, Sharon L., Gras, Stephanie, Archbold, Julia K., Tynan, Fleur E., Miles, John J., McCluskey, James, Burrows, Scott R., Rossjohn, Jamie, and Khanna, Rajiv (2008) Impact of clonal competition for peptide-MHC complexes on the CD8⁺ T-cell repertoire selection in a persistent viral infection. Blood, 111 (8). pp. 4283-4292.

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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.

Item ID:	45391
Item Type:	Article (Research - C1)
ISSN:	1528-0020
Funders:	National Health and Medical Research Council (NHMRC), Queensland Cancer Fund (QCF), Australian Research Council (ARC)
Date Deposited:	06 Sep 2016 23:48
FoR Codes:	11 MEDICAL AND HEALTH SCIENCES > 1107 Immunology > 110702 Applied Immunology (incl Antibody Engineering, Xenotransplantation and T-cell Therapies) @ 100%
SEO Codes:	92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920108 Immune System and Allergy @ 100%
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