The impact of TCR-binding properties and antigen presentation format on T cell responsiveness

Adam S. Chervin, Jennifer D. Stone, Phillip D. Holler, Ailin Bai, Jianzhu Chen, Herman N. Eisen, David M. Kranz

Research output: Contribution to journalArticle

Abstract

TCR interactions with cognate peptide-MHC (pepMHC) ligands are generally low affinity. This feature, together with the requirement for CD8/CD4 participation, has made it difficult to dissect relationships between TCR-binding parameters and T cell activation. Interpretations are further complicated when comparing different pepMHC, because these can vary greatly in stability. To examine the relationships between TCR-binding properties and T cell responses, in this study we characterized the interactions and activities mediated by a panel of TCRs that differed widely in their binding to the same pepMHC. Monovalent binding of soluble TCR was characterized by surface plasmon resonance, and T cell hybridomas that expressed these TCR, with or without CD8 coexpression, were tested for their binding of monomeric and oligomeric forms of the pepMHC and for subsequent responses (IL-2 release). The binding threshold for eliciting this response in the absence of CD8 (KD = 600 nM) exhibited a relatively sharp cutoff between full activity and no activity, consistent with a switchlike response to pepMHC on APCs. However, when the pepMHC was immobilized (plate bound), T cells with the lowest affinity TCRs (e.g., KD = 30 μM) responded, even in the absence of CD8, indicating that these TCR are signaling competent. Surprisingly, even cells that expressed high-affinity (KD = 16 nM) TCRs along with CD8 were unresponsive to oligomers in solution. The findings suggest that to drive downstream T cell responses, pepMHC must be presented in a form that supports formation of appropriate supramolecular clusters.

Original languageEnglish (US)
Pages (from-to)1166-1178
Number of pages13
JournalJournal of Immunology
Volume183
Issue number2
DOIs
StatePublished - Jul 15 2009

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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