Mixed functional characteristics correlating with TCR-ligand koff-rate of MHC-tetramer reactive T cells within the naive T-cell repertoire

Pleun Hombrink, Yotam Raz, Michel G.D. Kester, Renate De Boer, Bianca Weißbrich, Peter A. Von dem Borne, Dirk H. Busch, Ton N.M. Schumacher, J. H.Frederik Falkenburg, Mirjam H.M. Heemskerk

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

The low frequency of antigen-specific naïve T cells has challenged numerous laboratories to develop various techniques to study the naïve T-cell repertoire. Here, we combine the generation of naïve repertoire-derived antigen-specific T-cell lines based on MHC-tetramer staining and magnetic-bead enrichment with in-depth functional assessment of the isolated T cells. Cytomegalovirus (CMV) specific T-cell lines were generated from seronegative individuals. Generated T-cell lines consisted of a variety of immunodominant CMV-epitope-specific oligoclonal T-cell populations restricted to various HLA-molecules (HLA-A1, A2, B7, B8, and B40), and the functional and structural avidity of the CMV-specific T cells was studied. Although all CMV-specific T cells were isolated based on their reactivity toward a specific peptide-MHC complex, we observed a large variation in the functional avidity of the MHC-tetramer positive T-cell populations, which correlated with the structural avidity measured by the recently developed Streptamer koff-rate assay. Our data demonstrate that MHC-tetramer staining is not always predictive for specific T-cell reactivity, and challenge the sole use of MHC-tetramers as an indication of the peripheral T-cell repertoire, independent of the analysis of functional activity or structural avidity parameters.

Original languageEnglish
Pages (from-to)3038-3050
Number of pages13
JournalEuropean Journal of Immunology
Volume43
Issue number11
DOIs
StatePublished - Nov 2013

Keywords

  • CD8 T cells
  • Immune responses
  • MHC
  • Naive cells
  • TCR

Fingerprint

Dive into the research topics of 'Mixed functional characteristics correlating with TCR-ligand koff-rate of MHC-tetramer reactive T cells within the naive T-cell repertoire'. Together they form a unique fingerprint.

Cite this