Cytomegalovirus-specific CD8+ T cells targeting different peptide/HLA combinations demonstrate varying T-cell receptor diversity

Sandra Giest, Alasdair McWhinnie, Marie-Paule Lefranc, Ann-Margaret Little, Sarah Grace, Stephen Mackinnon, J Alejandro Madrigal, Paul J Travers

Research output: Contribution to journalArticlepeer-review

Abstract

Cytomegalovirus (CMV) infection and reactivation pose a serious threat for patients after haematopoietic stem cell transplantation. We have previously shown that CD8(+) T cells targeting different CMV epitopes correlate with protection at different threshold frequencies in those patients. To investigate if this may relate to a different quality of these cells here we analyse the T-cell receptor diversity of pp50 (245-253)/HLA-A*0101 specific CD8(+) T cells with that of CD8(+) T cells targeting various pp65 peptides. The results from this pilot study show differences in the breadth of the T-cell receptor usage of the different cell populations. We observe for the first time that the T-cell receptor Vβ CDR3 spectratypes used by CMV pp50 (245-253)/HLA-A*0101-specific CD8(+) T cells can reach higher numbers than those used by CD8(+) T cells targeting various pp65 peptides in our patient cohort. This merits further investigation into the effectiveness of the different CMV-specific T cells and their impact on immunosenescence, which is important to eventually define the most useful source of adoptive therapy and monitoring protocols for cytomegalovirus-specific immune responses.
Original languageEnglish
Pages (from-to)27-39
Number of pages13
JournalImmunology
Volume135
Issue number1
DOIs
Publication statusPublished - Jan 2012

Keywords

  • Viral Proteins
  • HLA-A1 Antigen
  • Receptors, Antigen, T-Cell, alpha-beta
  • DNA-Binding Proteins
  • Humans
  • Pilot Projects
  • Receptor-CD3 Complex, Antigen, T-Cell
  • Cytomegalovirus
  • Viral Matrix Proteins
  • Phosphoproteins
  • CD8-Positive T-Lymphocytes
  • Adult
  • Cohort Studies
  • Cytomegalovirus Infections
  • Middle Aged
  • Peptides
  • Female
  • Male

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