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Nonstimulatory peptides contribute to antigen-induced CD8–T cell receptor interaction at the immunological synapse

Nature Immunology volume 6, pages 785–792 (2005)Cite this article

Abstract

It is unclear if the interaction between CD8 and the T cell receptor (TCR)–CD3 complex is constitutive or antigen induced. Here, fluorescence resonance energy transfer microscopy between fluorescent chimeras of CD3ζ and CD8β showed that this interaction was induced by antigen recognition in the immunological synapse. Nonstimulatory endogenous or exogenous peptides presented simultaneously with antigenic peptides increased the CD8-TCR interaction. This finding indicates that the interaction between the intracellular regions of a TCR-CD3 complex recognizing its cognate peptide–major histocompatibility complex (MHC) antigen, and CD8 (plus the kinase Lck), is enhanced by a noncognate CD8-MHC interaction. Thus, the interaction of CD8 with a nonstimulatory peptide-MHC complex helps mediate T cell recognition of antigen, improving the coreceptor function of CD8.

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Figure 1: Function of fluorescent chimeric proteins.
Figure 2: T cell–APC conjugate formation and CD3ζ and CD8β recruitment to the synapse.
Figure 3: CD8 clustering to the synapse is MHC driven, whereas CD3ζ clustering is antigen driven.
Figure 4: Agonist peptide induces colocalization and interaction between CD8β-YFP and CD3ζ-CFP.
Figure 5: Close molecular proximity of CD8β and CD3ζ can be induced by pMHC molecules alone.
Figure 6: Nonstimulatory peptides increase antigen-induced interaction between CD8 and TCR.

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Acknowledgements

We thank S. Jameson (University of Minnesota, Minnesota) for the collection of endogenous H-2Kb-binding peptides; E. Palmer, R. Germain, G. Nolan and J. Altman for reagents; and W. Havran, L. Sherman and C. Lotz for critical reading of the manuscript. Supported by the National Institutes of Health (GM065230, DK61329 and GM039476 to N.R.J.G. and T32 AI07290 to T.Z.) and Scripps NeuroAIDS Preclinical Studies (P30MH62261). This is manuscript 16479-IMM from The Scripps Research Institute.

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  1. Tomasz Zal

    Present address: Department of Immunology, MD Anderson Cancer Center, University of Texas, Houston, Texas, 77030, USA

Authors and Affiliations

  1. Department of Immunology, IMM1, The Scripps Research Institute, La Jolla, 92037, California, USA

    Pia P Yachi, Jeanette Ampudia, Nicholas R J Gascoigne & Tomasz Zal

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Supplementary information

Supplementary Fig. 1

Example cells for CD3ζ and CD8β recruitment to the synapse. (PDF 1233 kb)

Supplementary Fig. 2

CD8c lustering to the synapse is MHC - driven. (PDF 199 kb)

Supplementary Fig. 3

Endogenous non-stimulatory peptides increase antigen - induced interaction between CD8 and TCR, T-APC conjugate formation, and TCR endocytosis. (PDF 943 kb)

Supplementary Methods (PDF 77 kb)

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Yachi, P., Ampudia, J., Gascoigne, N. et al. Nonstimulatory peptides contribute to antigen-induced CD8–T cell receptor interaction at the immunological synapse. Nat Immunol 6, 785–792 (2005). https://doi.org/10.1038/ni1220

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