alloreactive

Alloreactive refers to immune responses directed against alloantigens—antigens that differ between genetically non-identical individuals of the same species. In humans, alloreactivity most often involves reactions to donor antigens encountered during transplantation, but it can also occur in transfusion or pregnancy when foreign HLA or other polymorphic antigens are encountered. Alloreactive responses are primarily mediated by T cells and antibodies that recognize non-self surface molecules, especially human leukocyte antigens (HLA), but can involve other alloantigens as well.

In T cell–mediated alloreactivity, two major recognition pathways are described. Direct allorecognition occurs when recipient T cells survey donor antigen-presenting cells and recognize intact donor MHC molecules presenting peptides, leading to rapid, robust activation. Indirect allorecognition happens when recipient antigen-presenting cells process donor-derived antigens and present donor peptides on self MHC to T cells, producing a slower but sustained response. A semi-direct pathway, involving transfer of donor MHC onto recipient APCs, can bridge these processes. B cell–mediated alloreactivity involves alloantibodies against donor HLA antigens, which can drive antibody-mediated rejection and hyperacute rejection after transplantation.

Clinically, alloreactivity is a major barrier to solid organ and hematopoietic stem cell transplantation. It influences graft survival, graft-versus-host disease risk, and transfusion strategies. Assessment tools include crossmatching, HLA typing, and measurement of panel reactive antibodies, as well as functional assays like mixed lymphocyte reactions and T cell– or antibody–based tests to gauge the strength of alloreactive responses. Strategies to minimize alloreactivity include careful donor–recipient matching and immunosuppressive regimens.