Alloreactive cytotoxic T-cell function, peptide nonspecific

Abstract

The recognition requirements necessary for murine alloreactive cytotoxic T-cells to carry out their effector function has been investigated using target cells that express a unique class I major histocompatibility complex (MHC)-peptide pair. The human cell line T2 and the murine cell line RMA-S are defective in peptide transport components needed to effectively express stable MHC class I molecules at the cell surface. When T2 cells were infected with a vaccinia virus that encoded the K(d) gene and provided with a K(d)- motif peptide from the nucleoprotein of influenza virus (NPP), these cells could be lysed by polyclonal allo K(d)-reactive cytotoxic T-lymphocytes (CTL). Similar results were obtained with the murine RMA-S-K(d) cell line, transfected with cDNA able to express some 'empty' K(d) that is heat-labile. Adding another K(d)-motif peptide from influenza virus haemagglutinin (HAP) stabilized the surface expression of K(d) and allowed the RMA-S-K(d) cells to be lysed before or after heat shock. At 27 °C anti-K(d) alloreactive CTL- lysed target cells in the presence and absence of HAP peptide. Alloreactive CTL appear to have a more stringent requirement for a high density of MHC class I on cell surfaces relative to peptide-specific MHC-restricted CTL. We conclude that while K(d)-restricted CTL activity is strictly peptide- specific, anti-K(d)-specific alloreactivity is MHC allele-specific, but peptide-nonspecific. This conclusion is at odds with the Standard Model of T- cell receptor (TCR) function, but consistent with the predictions of a Competing Model of TCR function. Show more