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Soluble MHC Class I Molecules Induce Cellular Death in a CD8+ T-cell Hybridoma Tumor Model

Soluble MHC Class I Molecules Induce Cellular Death in a CD8+ T-cell Hybridoma Tumor Model

T Kambayashi, F Ichihara, P E Jensen, H G Ljunggren

Int J Cancer. 2001 Feb 1;91(3):373-8.

PMID: 11169962

Abstract:

T cells undergo activation-induced cell death (AICD) after T-cell receptor cross-linking in the absence of co-stimulation. In this study, we examined whether AICD induced by purified MHC class I molecules could be used to selectively eliminate tumor cells in T-cell malignancies. As a model, soluble H-2K(b) molecules refolded with the chicken ovalbumin SIINFEKL peptide (K(b)-OVA) and a CD8+ T-cell hybridoma (CD8-OVA) specific for this peptide were used. Addition of CD8-OVA hybridoma cells to plastic plates adsorbed with K(b)-OVA molecules resulted in a concentration-dependent decrease in cellular proliferation. Exogenous IL-4 further depressed the proliferation of CD8-OVA cells in a dose-dependent manner in the presence, but not in the absence, of K(b)-OVA. Staining of these cells with propidium iodide confirmed that the decrease in cellular proliferation was due to apoptosis. The cytotoxic effect of plastic-immobilized K(b)-OVA could be mimicked by soluble K(b)-OVA tetramers. Furthermore, co-injection of K(b)-OVA tetramers and CD8-OVA cells into mice suppressed the tumorigenicity of CD8-OVA cells. In conclusion, we describe a system whereby soluble MHC class I molecules can be used to selectively induce cellular death in a monoclonal T-cell tumor model. With future development, the use of MHC molecules may help to eliminate specific T cells in cases of T-cell malignancy and auto-immunity.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
ALP138831864	Ovalbumin (257-264) chicken		138831-86-4 (free base)	Price

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