Journal
JOURNAL OF IMMUNOLOGY
Volume 167, Issue 5, Pages 2555-2560Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.167.5.2555
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Funding
- NCI NIH HHS [CA-14599] Funding Source: Medline
- NIAID NIH HHS [P01 AI 35294] Funding Source: Medline
- NIDDK NIH HHS [P01-DK49799] Funding Source: Medline
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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 C-chain and recruitment and phosphorylation of xi -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.
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