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Immunodominance Hierarchies and Gender Bias in Direct T CD8 ‐Cell Alloreactivity
Author(s) -
Mifsud N. A.,
Purcell A. W.,
Chen W.,
Holdsworth R.,
Tait B. D.,
McCluskey J.
Publication year - 2008
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2007.02044.x
Subject(s) - immunodominance , immunology , context (archaeology) , cd8 , immunosuppression , human leukocyte antigen , major histocompatibility complex , transplantation , t cell , medicine , histocompatibility testing , cytotoxic t cell , antigen , immune system , biology , in vitro , genetics , paleontology
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 HLA mismatches are equivalent in their stimulation of allogeneic T cells making it important to determine which of these might be more significant as predictors of allograft rejection. To this end, we used defined antigen‐presenting cell (APC) transfectants expressing single MHC‐I allotypes as target cells that could discriminate the relative contribution of individual mismatched MHC‐I allotypes to direct T‐cell alloreactivity. We demonstrate remarkably reproducible patterns of immunodominance in reactivity across mismatched MHC‐I allotypes. These patterns are HLA context‐dependent, partly reflecting alloantigenic competition in responder cell responses. In strong alloresponses, we also observed an increased percentage of alloreactive T CD8 cells in female responders, regardless of the stimulator gender, highlighting HLA‐independent factors in the potency of the alloresponse. This approach provides a potential measure of specific alloreactive T cells that could be used in clinical practice for selection of donors, assessment of posttransplant outcomes, modulation of immunosuppression and detection of rejection episodes.