REJECTION OF TUMORS IN MICE WITH SEVERE COMBINED IMMUNODEFICIENCY SYNDROME DETERMINED BY THE MAJOR HISTOCOMPATIBILITY COMPLEX CLASS-I EXPRESSION ON THE GRAFT

This study addresses the role of MHC class I molecules in the rejectio n of tumor grafts by SCID mice. Tumor cell lines, their corresponding MHC class I transfectants, and MHC class I-deficient mutants were inoc ulated to SCID mice. This allowed a study of tumor rejection responses in an environment with normal numbers of natural killer cells but lar gely devoid of functional T and B cells. C.B-17 (H-2(d)) SCID) mice we re found to reject low (10(2)) but not high (10(4)) doses of allogenei c (H-2(b)) tumor cells. The introduction of H-2D(d) into such allogene ic tumor cells abrogated the rejection response with progressive tumor growth as a consequence. Introduction of H-2K(d) or L(d) had no or on ly marginal effects. The protective ability of H-2D(d) was mapped to t he alpha 1/alpha 2 domains of the molecule. H-2D(d) protected allogene ic tumors from rejection also in C3H SCID mice of the H-2(k) haplotype , demonstrating that this ability was not dependent on H-2D(d) express ion in the host. Expression of endogenous H-2K(b) and/or D-b molecules partially protected wild-type allogeneic tumor cells from rejection s ince mutant allogeneic cells, devoid of class I expression, were rejec ted even after high-dose inoculation. Introduction of either allogenei c or xenogeneic class I molecules did not lead to rejection of otherwi se MHC class I syngeneic (H-2(d)) tumor cells. The observed tumor cell rejection in SCID mice was dependent on natural killer cells. After d epletion of asialo-GM1+ cells, all inoculated tumor cell lines grew pr ogressively, independently of MHC class I expression. These results ar e compatible with a model where expression of certain, but not all, cl ass I molecules protect from natural killer cell-mediated rejection. T here was no evidence for rejection occurring as a consequence of the e xpression of allogeneic or xenogeneic class I molecules on the grafted cells. MHC class I expression may thus influence tumor cell recogniti on in mice lacking T-cell receptor expression.