Abstract
Since the discovery of T cells that express two T cell receptors (TCRs), termed dual TCR cells, most studies have focused on their autoimmune potential, while their beneficial roles remained elusive. We identified, in normal mice, dual TCR cells that participated in the immune response to a foreign antigen. Unlike single TCR cells, dual TCR cells used the nonselected TCR to respond in the periphery, but relied on coexpression of a second TCR for intrathymic selection. We found that they were selected at low frequency in the naïve repertoire, but dominated the response to antigen through clonal expansion. Thus, dual TCR cells can extend the TCR repertoire for foreign antigens by rescuing functional TCRs that cannot be selected on single TCR cells; they can, therefore, benefit the immune system.
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Acknowledgements
We thank N. Crispe for critical comments on the manuscript; D. Sant'Angelo for advice; G. Losyev for help on screening mice; D. Mathis and C. Benoist for pTα and pTβ cassette vectors. Supported in part by NIH grants (AI-26791, CA-28250 to K. B., and AI-14579 to C. J.), and by the Howard Hughes Medical Institute.
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Web Figure 1.
KB TCR is not positively selected in the αTg×KB RAG-1−/− thymus. The αTg was derived from the T cell hybrid T200.4E. The αTg×KB RAG-1−/− thymus was from mice that expressed both the αTg and the KB αβTCR on the RAG-1−/− background. Coexpression of the second αTg will reduce the expression level of KB TCR. We found no positive selection in the thymus: lack of CD4 single positive T cells (<1%); no mature CD4+ cells (<1%) in Vβ8hi-gated post-selection thymocytes; and a normal number of total thymocytes (75×106 cells) with majority being the immature CD4+CD8+ cells (82%). CD4 and CD8 distributions are shown as a dot-plot without (left) and with (right) electronic gating on Vβ8hi thymocytes. The expression of the KB TCRβ chain (Vβ8) is shown as a histogram. Single-cell suspensions of the thymus were triple stained for CD4, CD8 and Vβ8. The profiles are representative of two experiments. (GIF 16 kb)
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He, X., Janeway, C., Levine, M. et al. Dual receptor T cells extend the immune repertoire for foreign antigens. Nat Immunol 3, 127–134 (2002). https://doi.org/10.1038/ni751
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DOI: https://doi.org/10.1038/ni751
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