Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy

• Published in: Nature (London) 1986-02, Vol.319 (6055), p.675-678
• Main Authors: Kärre, Klas, Ljunggren, Hans Gustaf, Piontek, Gerald, Kiessling, Rolf
• Format: Article
• Language: English
• Subjects: Animals; Graft Rejection; H-2 Antigens - immunology; Humanities and Social Sciences; Immune Tolerance; Immunity, Innate; Killer Cells, Natural - immunology; letter; Lymphoma - immunology; Major Histocompatibility Complex; Mice; multidisciplinary; Neoplasm Transplantation; Science; Science (multidisciplinary)
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/319675a0

Metazoan organisms may discriminate between self and non-self not only by the presence of foreign antigens but also by the absence of normal self markers 1 . Mammalian adaptive immune responses use the first strategy, with the additional requirement that foreign antigens are recognized in the context of self-major histocompatibility complex (MHC) products at the cell surface 2 . Aberrant cells which fail to express MHC products adequately can therefore avoid detection 2–4 . A more primitive but complementary defence system, eliminating such cells on the basis of absent self-markers, is suggested by a re-interpretation 5,6 of phenomena associated with metastasis and natural resistance. We now show that murine lymphoma cells selected for loss of H–2 expression are less malignant after low-dose inoculation in syngeneic hosts than are wild-type cells, and that the rejection of such cells is non-adaptive. On the basis of our data, we suggest that natural killer cells are effector cells in a defence system geared to detect the deleted or reduced expression of self-MHC.