Alien antigens return to the fold

Theories rationalizing major histocompatibility complex (MHC) class I polymorphism and the high frequency of alloreactive T lymphocytes initiated the search for expression of genetically inappropriate MHC class I molecules by tumour cells. Many examples of such 'Alien Antigens' have been reported in the past fifteen years. Some were previously shown to result from a variety of serological artefacts. Recent papers describe structural and genetic analysis of two extensively studied and outstanding systems. In both cases the Alien Antigens are also artefacts, resulting from genetic heterogeneity in either mice or cell lines. No Alien Antigens have survived rigorous evaluation and they are unlikely to constitute a significant biological phenomenon. It is also unlikely that the successive experimental plagues that created the Alien Antigens are unique to this corner of tumour immunology. Sophisticated innovation in experimental systems makes much immunological investigation increasingly dependent on the genetic integrity of mice and cell lines.