Low-affinity CD4+ T cells are major responders in the primary immune response

Ryan J. Martinez, Rakieb Andargachew, Hunter A. Martinez and Brian D. Evavold ()
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Ryan J. Martinez: Emory University
Rakieb Andargachew: Emory University
Hunter A. Martinez: Emory University
Brian D. Evavold: Emory University

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: Abstract A robust primary immune response has been correlated with the precursor number of antigen-specific T cells, as identified using peptide MHCII tetramers. However, these tetramers identify only the highest-affinity T cells. Here we show the entire CD4+ T-cell repertoire, inclusive of low-affinity T cells missed by tetramers, using a T-cell receptor (TCR) signalling reporter and micropipette assay to quantify naive precursors and expanded populations. In vivo limiting dilution assays reveal hundreds more precursor T cells than previously thought, with higher-affinity tetramer-positive T cells, comprising only 5–30% of the total antigen-specific naive repertoire. Lower-affinity T cells maintain their predominance as the primary immune response progresses, with no enhancement of survival of T cells with high-affinity TCRs. These findings demonstrate that affinity for antigen does not control CD4+ T-cell entry into the primary immune response, as a diverse range in affinity is maintained from precursor through peak of T-cell expansion.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13848

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DOI: 10.1038/ncomms13848

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