Alloreactive cytotoxic T-Cell function, peptide nonspecific

The recognition requirements necessary for murine alloreactive cytotoxic T- cells to carry out their effector function has been investigated using targ et cells that express a unique class I major histocompatibility complex (MH C)-peptide pair. The human cell line T2 and the murine cell line RMA-S are defective in peptide transport components needed to effectively express sta ble 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-mot if peptide from the nucleoprotein of influenza virus (NPP), these cells cou ld 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, transfec ted with cDNA able to express some 'empty' K-d that is heat-labile. Adding another K-d-motif peptide from influenza virus haemagglutinin (HAP) stabili zed the surface expression of K-d and allowed the RMA-S-K-d cells to be lys ed before or after heat shock. At 27 degrees C anti-K-d alloreactive CTL-ly sed target cells in the presence and absence of HAP peptide. Alloreactive C TL appear to have a more stringent requirement for a high density of MHC cl ass I on cell surfaces relative to peptide-specific MHC-restricted CTL. We conclude that while K-d-restricted CTL activity is strictly peptide-specifi c, anti-K-d-specific alloreactivity is MHC allele-specific, but peptide-non specific. This conclusion is at odds with the Standard Model of T-cell rece ptor (TCR) function, but consistent with the predictions of a Competing Mod el of TCR function.