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Alloreactive Cytotoxic T‐Cell Function, Peptide Nonspecific
Author(s) -
Arno Müllbacher,
Mario Lobigs,
Ferdynand J. Kos,
Rodney E. Langman
Publication year - 1999
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1046/j.1365-3083.1999.00568.x
Subject(s) - cytotoxic t cell , ctl* , major histocompatibility complex , biology , mhc class i , mhc restriction , t cell , microbiology and biotechnology , streptamer , t cell receptor , virology , antigen presenting cell , antigen , immune system , immunology , in vitro , biochemistry
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.