Immunodominance Hierarchies and Gender Bias in Direct TCD8-Cell Alloreactivity

摘要: Allogeneic solid organ transplantation often occurs across multiple donor–recipient HLA mismatches with consequent risk of allograft rejection. However, there is growing evidence that not all are equivalent in their stimulation allogeneic T cells making it important to determine which these might be more significant as predictors To this end, we used defined antigen-presenting cell (APC) transfectants expressing single MHC-I allotypes target could discriminate the relative contribution individual mismatched direct T-cell alloreactivity. We demonstrate remarkably reproducible patterns immunodominance reactivity allotypes. These context-dependent, partly reflecting alloantigenic competition responder responses. In strong alloresponses, also observed an increased percentage alloreactive TCD8 female responders, regardless stimulator gender, highlighting HLA-independent factors potency alloresponse. This approach provides a potential measure specific clinical practice for selection donors, assessment posttransplant outcomes, modulation immunosuppression and detection rejection episodes.