Antigen-specific blockade of T cells in vivo using dimeric MHC peptide

S. M. O'Herrin, J. E. Slansky, Q. Tang, M. A. Markiewicz, T. F. Gajewski, D. M. Pardoll, J. P. Schneck, J. A. Bluestone

Research output: Contribution to journalArticlepeer-review

Abstract

Ag-specific immune tolerance in clinical organ transplantation is currently an unrealized but critical goal of transplant biology. The specificity and avidity of multimerized MHC-peptide complexes suggests their potential ability to modulate T cell sensitization and effector functions. In this study, we examined the ability of MHC-peptide dimers to modulate T cell function both in vitro and in vivo. Soluble MHC dimers induced modulation of surface TCR expression and inhibited T cell cytolytic activity at nanomolar concentrations in vitro. Furthermore, engagement of TCR by soluble dimers resulted in phosphorylation of the TCR ζ-chain and recruitment and phosphorylation of ζ-associated protein-70 to the signaling complex, the latter of which increased upon dimer cross-linking. Significantly, Ag-specific inhibition of an alloreactive TCR-transgenic T cell population in vivo resulted in consequent outgrowth of an allogeneic tumor. The prolonged Ag-specific suppression of expansion and/or effector function of cognate T cells in vivo suggests that soluble MHC dimers may be a means of inducing sustained Ag-specific T cell unresponsiveness in vivo.

Original languageEnglish (US)
Pages (from-to)2555-2560
Number of pages6
JournalJournal of Immunology
Volume167
Issue number5
DOIs
StatePublished - Sep 1 2001
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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