xenoantigenicity

Xenoantigenicity is the immunological propensity of antigens from one species to provoke an immune response when encountered in another species. It is a central concept in xenotransplantation, where tissues or cells from animals are transplanted into humans or other recipients. The degree of xenoantigenicity reflects species differences in surface molecules, particularly glycan structures, and can influence both humoral and cellular immune reactions.

The strongest responses typically arise from naturally occurring antibodies against xenogeneic carbohydrate epitopes, notably the Gal alpha-1,3-Gal (α-Gal) determinant found on many non-primate mammals. In humans, anti-α-Gal antibodies can mediate rapid complement activation and hyperacute rejection of pig or other animal tissues. Other xenoantigens, such as Neu5Gc and certain Sd(a)-related glycans, contribute to residual reactivity. Beyond antibodies, xenogeneic antigens can be processed and presented by antigen-presenting cells, eliciting T-cell responses, while innate effectors like natural killer cells and macrophages participate in rejection processes. Xenoantigenicity thus depends on the species pair, tissue type, and the glycosylation patterns of donor tissue.

Strategies to reduce xenoantigenicity include genetic modification of donor animals to remove major xenoantigens and to express human regulatory proteins that dampen immune activation or coagulation. Other approaches involve selective immunosuppression and tolerance induction, as well as using decellularized or encapsulated tissues. Preclinical and clinical xenotransplantation research also weighs the risk of zoonotic infection, including endogenous retroviruses, and emphasizes careful screening and biosafety measures.

Assessment of xenoantigenicity relies on serological assays, flow cytometry, and functional tests to quantify xenoantibody binding and complement-mediated injury, guiding donor selection and therapeutic planning.