xenoantigens

Xenoantigen is an antigen derived from a different species that is recognized as foreign by the immune system of another species. The term is mainly used in xenotransplantation and cross-species transfusion contexts to describe molecules on donor tissues that can stimulate an immune response in the recipient. Xenoantigens are distinct from alloantigens (between individuals of the same species) and autoantigens (self).

In xenotransplantation, xenoantigens on donor organs or tissues can provoke hyperacute and acute immune rejection. Preformed antibodies in the recipient can bind these antigens, activating the complement system and leading to rapid tissue injury. Cellular immune responses can also contribute to rejection. The most studied xenoantigen in pig-to-human transplantation is the alpha-Gal epitope (Galα1-3Gal). Humans commonly have natural antibodies against this carbohydrate, which has driven efforts to reduce xenoantigenicity through genetic modification of donor animals.

Other potential xenoantigens of interest include non-Gal carbohydrate antigens such as Neu5Gc and Sd(a)-family determinants. Research in this area often focuses on reducing or removing xenoantigens through genetic engineering (for example, knockout of GGTA1 to eliminate Gal and introduction of human immune-regulatory genes), as well as approaches to tolerate or modulate the recipient’s immune response.

Detection and management of xenoantigens involve serological testing, crossmatching, and consideration of immunosuppressive or tolerance-inducing strategies. Xenoantigens remain a central challenge in xenotransplantation and in the broader use of cross-species biological materials.