PMID: 7582905Jun 1, 1995Paper

Viral peptide specific cytotoxic T lymphocytes are of high avidity to host-MHC but only low avidity to donor-MHC after allogeneic bone marrow transplantation

Transplant Immunology
D Kyburz, D E Speiser


In the thymus maturing T lymphocytes are positively selected for efficient interaction with self-MHC molecules. Consequently, mature peripheral T cells recognize foreign (microbial) antigens in association with self-MHC molecules (known as MHC restricted recognition). In experimental bone marrow transplantation (BMT) lymphohaemopoietic stem cells from an MHC disparate donor transfused to an irradiated host give rise to mature T lymphocytes with host-MHC restriction specificity. While experiments with T cell receptor transgenic mice have largely confirmed this concept, many studies using genetically unmanipulated animals analysing polyclonal T cell repertoires have also shown donor-MHC restricted T cell activities after allogeneic BMT. To analyse this discrepancy we generated 18 virus specific cytotoxic T cell (CTL) clones, 16 from F1 into parent and two from fully allogeneic bone marrow chimeras, and analysed the MHC restriction specificity in proliferation and cytotoxicity assays. The cytotoxicity of all the clones was primarily host-MHC restricted. However, the CTL clones proliferated to viral antigen presented by both donor- or host-MHC. Our model allowed CTL cloning by cross-specific stimulation with antigen plus either don...Continue Reading


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