Abstract
To test the hypothesis that major histocompatibility complex (MHC) molecules protect target cells from lysis by natural killer cells (NKC), we transfected the MHC- B16 melanoma line F10 with the class I genes encoding Dd, Kb, and Kk. Only low levels of Dd expression could be obtained and there was no protection against NKC. By contrast, Kb and Kk transfectants were obtained which displayed significant resistance to NKC, and with the latter transfectants resistance was clearly related to the level of transgene expression. Various mutants of the F10 line with altered patterns of MHC expression were also obtained. These mutant lines provided evidence that (i) the Db molecule is also capable of inducing resistance to NKC and (ii) high MHC class I expression does not by itself guarantee lowered susceptibility to NKC.
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Selected References
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- Arnold B., Burgert H. G., Hamann U., Hämmerling G., Kees U., Kvist S. Cytolytic T cells recognize the two amino-terminal domains of H-2 K antigens in tandem in influenza A infected cells. Cell. 1984 Aug;38(1):79–87. doi: 10.1016/0092-8674(84)90528-2. [DOI] [PubMed] [Google Scholar]
- Bennett M. Biology and genetics of hybrid resistance. Adv Immunol. 1987;41:333–445. doi: 10.1016/s0065-2776(08)60034-6. [DOI] [PubMed] [Google Scholar]
- Bordignon C., Daley J. P., Nakamura I. Hematopoietic histoincompatibility reactions by NK cells in vitro: model for genetic resistance to marrow grafts. Science. 1985 Dec 20;230(4732):1398–1401. doi: 10.1126/science.3906897. [DOI] [PubMed] [Google Scholar]
- Brooks C. G., Flannery G. R. Quantitative studies of natural immunity to solid tumours in rats. Persistence of natural immunity throughout reproductive life, and absence of suppressor cells in infant rats. Immunology. 1980 Feb;39(2):187–194. [PMC free article] [PubMed] [Google Scholar]
- Brooks C. G., Urdal D. L., Henney C. S. Lymphokine-driven "differentiation" of cytotoxic T-cell clones into cells with NK-like specificity: correlations with display of membrane macromolecules. Immunol Rev. 1983;72:43–72. doi: 10.1111/j.1600-065x.1983.tb01072.x. [DOI] [PubMed] [Google Scholar]
- Carlow D. A., Payne U., Hozumi N., Roder J. C., Czitrom A. A. Class I (H-2Kb) gene transfection reduces susceptibility of YAC-1 lymphoma targets to natural killer cells. Eur J Immunol. 1990 Apr;20(4):841–846. doi: 10.1002/eji.1830200419. [DOI] [PubMed] [Google Scholar]
- Dennert G., Landon C., Lord E. M., Bahler D. W., Frelinger J. G. Lysis of a lung carcinoma by poly I:C-induced natural killer cells is independent of the expression of class I histocompatibility antigens. J Immunol. 1988 Apr 1;140(7):2472–2475. [PubMed] [Google Scholar]
- Evans G. A., Margulies D. H., Shykind B., Seidman J. G., Ozato K. Exon shuffling: mapping polymorphic determinants on hybrid mouse transplantation antigens. Nature. 1982 Dec 23;300(5894):755–757. doi: 10.1038/300755a0. [DOI] [PubMed] [Google Scholar]
- Gopas J., Segal S., Hammerling G., Bar-Eli M., Rager-Zisman B. Influence of H-2K transfection on susceptibility of fibrosarcoma tumor cells to natural killer (NK) cells. Immunol Lett. 1988 Mar;17(3):261–265. doi: 10.1016/0165-2478(88)90039-9. [DOI] [PubMed] [Google Scholar]
- Kiessling R., Hochman P. S., Haller O., Shearer G. M., Wigzell H., Cudkowicz G. Evidence for a similar or common mechanism for natural killer cell activity and resistance to hemopoietic grafts. Eur J Immunol. 1977 Sep;7(9):655–663. doi: 10.1002/eji.1830070915. [DOI] [PubMed] [Google Scholar]
- Kärre K., Ljunggren H. G., Piontek G., Kiessling R. Selective rejection of H-2-deficient lymphoma variants suggests alternative immune defence strategy. Nature. 1986 Feb 20;319(6055):675–678. doi: 10.1038/319675a0. [DOI] [PubMed] [Google Scholar]
- Leiden J. M., Karpinski B. A., Gottschalk L., Kornbluth J. Susceptibility to natural killer cell-mediated cytolysis is independent of the level of target cell class I HLA expression. J Immunol. 1989 Mar 15;142(6):2140–2147. [PubMed] [Google Scholar]
- Ljunggren H. G., Sturmhöfel K., Wolpert E., Hämmerling G. J., Kärre K. Transfection of beta 2-microglobulin restores IFN-mediated protection from natural killer cell lysis in YAC-1 lymphoma variants. J Immunol. 1990 Jul 1;145(1):380–386. [PubMed] [Google Scholar]
- Murphy W. J., Kumar V., Bennett M. Rejection of bone marrow allografts by mice with severe combined immune deficiency (SCID). Evidence that natural killer cells can mediate the specificity of marrow graft rejection. J Exp Med. 1987 Apr 1;165(4):1212–1217. doi: 10.1084/jem.165.4.1212. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nishimura M. I., Stroynowski I., Hood L., Ostrand-Rosenberg S. H-2Kb antigen expression has no effect on natural killer susceptibility and tumorigenicity of a murine hepatoma. J Immunol. 1988 Dec 15;141(12):4403–4409. [PubMed] [Google Scholar]
- Ozato K., Mayer N., Sachs D. H. Hybridoma cell lines secreting monoclonal antibodies to mouse H-2 and Ia antigens. J Immunol. 1980 Feb;124(2):533–540. [PubMed] [Google Scholar]
- Ozato K., Sachs D. H. Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression. J Immunol. 1981 Jan;126(1):317–321. [PubMed] [Google Scholar]
- Piontek G. E., Taniguchi K., Ljunggren H. G., Grönberg A., Kiessling R., Klein G., Kärre K. YAC-1 MHC class I variants reveal an association between decreased NK sensitivity and increased H-2 expression after interferon treatment or in vivo passage. J Immunol. 1985 Dec;135(6):4281–4288. [PubMed] [Google Scholar]
- Rebai N., Mercier P., Kristensen T., Devaux C., Malissen B., Mawas C., Pierres M. Murine H-2Dd-reactive monoclonal antibodies recognize shared antigenic determinant(s) on human HLA-B7 or HLA-B27 molecules or both. Immunogenetics. 1983;17(4):357–370. doi: 10.1007/BF00372455. [DOI] [PubMed] [Google Scholar]
- Reiter Z., Fischer D. G., Rubinstein M. The protective effect of interferon against natural killing activity is not mediated via the expression of class I MHC antigens. Immunol Lett. 1988 Apr;17(4):323–328. doi: 10.1016/0165-2478(88)90005-3. [DOI] [PubMed] [Google Scholar]
- Rolstad B., Fossum S. Allogeneic lymphocyte cytotoxicity (ALC) in rats: establishment of an in vitro assay, and direct evidence that cells with natural killer (NK) activity are involved in ALC. Immunology. 1987 Feb;60(2):151–157. [PMC free article] [PubMed] [Google Scholar]
- Shimizu Y., DeMars R. Demonstration by class I gene transfer that reduced susceptibility of human cells to natural killer cell-mediated lysis is inversely correlated with HLA class I antigen expression. Eur J Immunol. 1989 Mar;19(3):447–451. doi: 10.1002/eji.1830190306. [DOI] [PubMed] [Google Scholar]
- Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
- Storkus W. J., Alexander J., Payne J. A., Cresswell P., Dawson J. R. The alpha 1/alpha 2 domains of class I HLA molecules confer resistance to natural killing. J Immunol. 1989 Dec 1;143(11):3853–3857. [PubMed] [Google Scholar]
- Storkus W. J., Alexander J., Payne J. A., Dawson J. R., Cresswell P. Reversal of natural killing susceptibility in target cells expressing transfected class I HLA genes. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2361–2364. doi: 10.1073/pnas.86.7.2361. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sturmhöfel K., Hämmerling G. J. Reconstitution of H-2 class I expression by gene transfection decreases susceptibility to natural killer cells of an EL4 class I loss variant. Eur J Immunol. 1990 Jan;20(1):171–177. doi: 10.1002/eji.1830200125. [DOI] [PubMed] [Google Scholar]
- Suzuki N., Bianchi E., Bass H., Suzuki T., Bender J., Pardi R., Brenner C. A., Larrick J. W., Engleman E. G. Natural killer lines and clones with apparent antigen specificity. J Exp Med. 1990 Aug 1;172(2):457–462. doi: 10.1084/jem.172.2.457. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tada N., Kimura S., Hatzfeld A., Hämmerling U. Ly-m11: the H-3 region of mouse chromosome 2 controls a new surface alloantigen. Immunogenetics. 1980;11(5):441–449. doi: 10.1007/BF01567813. [DOI] [PubMed] [Google Scholar]
- Tutt M. M., Kuziel W. A., Hackett J., Jr, Bennett M., Tucker P. W., Kumar V. Murine natural killer cells do not express functional transcripts of the alpha-, beta-, or gamma-chain genes of the T cell receptor. J Immunol. 1986 Nov 1;137(9):2998–3001. [PubMed] [Google Scholar]
