Molecular analysis of mouse major histocompatibility complex class I gene expression of tumors growing in the brain
Yamasaki, T.; Kikuchi, H.; Yamashita, J.; Kärre, K.; Ljunggren, H.G.; Klein, G.
No Shinkei Geka. Neurological Surgery 17(3): 229-237
1989
ISSN/ISBN: 0301-2603 PMID: 2505151 Document Number: 335870
The authors have investigated the regulation of mouse major histocompatibility complex (MHC, H-2) class I gene expression of tumors growing in the brain, by using T-cell lymphoma (Moloney leukemia virus-induced YAC-1 of A/Sn mouse origin) and its cell surface H-2 negative variants, A. H-2- and .beta.2m-. FACS analysis showed that low H-2 expressing YAC-1 markedly increased H-2 Kk, Dd and beta-2 microglobulin (.beta. 2m) induction on the cell surface after intracerebral (i. c.) passage, while there was no change in phenotypical expression of both A. H-2- and .beta. 2m-. Southern and Northern blot analyses revealed that the enhancement of H-2 class I expression in YAC-1 was due to transcriptional control of H-2 DNA genes. .beta. 2m- was confirmed to lack .beta. 2m- gene, causing cell surface H-2 negative expression. Immunoprecipitation method showed that, despite increase in mRNA of the H-2 gene, A. H-2- disclosed no class I H-2 expression because of the incapability of intracellular association of polypeptides between H-2 and .beta. 2m in the post-translational level. The H-2 class I expression on YAC-1 cells could also be induced by interferon gamma (IFN) in a dose-dependent manner in the range of 1 to 100 U/ml. At 100 U/ml, the H-2 inducing effect, regulated at the transcriptional level, was comparable to that observed after i. c. passage. In contrast, the A. H-2- and .beta. 2m- remained completely negative after IFN treatment. Furthermore, there was no significant change in other T cell differentiation antigens such as Thy-1, Lyt-1, Lyt-2 and L3T4 after i. c. passage as well as IFN treatment on either cell line. It is noted that the YAC-1 cells switched to the H-2 high phenotype either in mice injected i. v. with asialo-GM 1 antibodies or in thymectomized mice. On the contrary, the H-2 enhancement of YAC-1 was seen neither in sucking, irradiated nor cyclophosphamide-injected mice. Thus, it was suggested that IFN rather than T or NK cells might be directly related to transcriptional control of H-2 class I mRNA expression in YAC-1 cells and that functioning and mature immune system may be required for the cell surface H-2 enhancement. The role of H-2 class I enhancement in tumorigenicity is also discussed.