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Author Notes:

Correspondence and requests for materials should be addressed to G.K. (email: george.kassiotis@crick.ac.uk).

J.M. performed and interpreted experiments and wrote the manuscript.

M.J.P., U.E., G.T. and A.F. performed and interpreted experiments.

R.A. and B.E. designed, performed and interpreted experiments relating to two-dimensional TCR affinity measurements.

M.P. designed, prepared and provided the MHC II tetramer used in this study.

G.K. designed and interpreted the experiments, wrote the manuscript and supervised the study.

We wish to thank Dr Kristin A. Hogquist for the Nur77-GFP mice, Dr Toshitada Takemori for the conditional Bcl6 mice, Dr Kim Hasenkrug for FV and FBL-3 stocks, Dr Ulf Dittmer for the Ad5.pIX-gp70 stocks and Drs Anne O'Garra, Brigitta Stockinger, Mark Wilson and Eva Frickel for helpful comments and discussion. We are grateful for assistance from the Biological Services, Flow Cytometry and Protein Purification Facilities at the Francis Crick institute.

Accession codes: The Sequence Read Archive (SRA) and European Nucleotide Archive (ENA) accession numbers for the TCR sequences reported in this paper are SRX750575 and PRJEB11747, respectively.

Subject:

Research Funding:

This work was supported by the Francis Crick Institute which receives its core funding from Cancer Research UK, the UK Medical Research Council (U117581330 to G.K.), and the Wellcome Trust.

Keywords:

  • Science & Technology
  • Multidisciplinary Sciences
  • B cells
  • CD4-positive T cells
  • Cell death and immune response
  • Viral infection

Stepwise B-cell-dependent expansion of T helper clonotypes diversifies the T-cell response

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Journal Title:

Nature Communications

Volume:

Volume 7

Publisher:

, Pages 10281-10281

Type of Work:

Article | Final Publisher PDF

Abstract:

Antigen receptor diversity underpins adaptive immunity by providing the ground for clonal selection of lymphocytes with the appropriate antigen reactivity. Current models attribute T cell clonal selection during the immune response to T-cell receptor (TCR) affinity for either foreign or self peptides. Here, we report that clonal selection of CD4+ T cells is also extrinsically regulated by B cells. In response to viral infection, the antigen-specific TCR repertoire is progressively diversified by staggered clonotypic expansion, according to functional avidity, which correlates with self-reactivity. Clonal expansion of lower-avidity T-cell clonotypes depends on availability of MHC II-expressing B cells, in turn influenced by B-cell activation. B cells clonotypically diversify the CD4+ T-cell response also to vaccination or tumour challenge, revealing a common effect.

Copyright information:

© 2016, Nature Publishing Group.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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