Somatic variation of H-2Kk expression and structure in a T-cell lymphoma: instability, stabilization, high production and structural mutation.

Holtkamp, Bodo; Cramer, Matthias; Rajewsky, Klaus

doi:10.1002/j.1460-2075.1983.tb01683.x

Cited by 11 publications

(6 citation statements)

References 28 publications

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“…The differences vary from quantitative change to qualitative modification, as exemplified in several tumor cells that expressed attenuated structures of alien specificities distinct from those of their normal counterparts (6,7). These alterations could be caused by mutation, recombination, or activation of normal MHC genes (8,9). Recent studies on human and mouse liver tissues indicated that neither class I nor class II MHC antigens were detectable on the surface of normal hepatocytes (10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Expression of class I and class II major histocompatibility antigens on human hepatocellular carcinoma.

Sung¹,

Hu²,

Hsu³

et al. 1989

J. Clin. Invest.

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Previous reports indicate that human hepatocytes do not express class I and class II MHC antigens. Our analyses on 10 human hepatocellular carcinoma (HCC) cell lines by immunofluorescence tests and RIA, demonstrate that all the human HCC cell lines tested express class I MHC antigens and among them, three poorly differentiated human HCC cell lines also express class II MHC antigens. Results of immunoprecipitation and/or Western blotting experiments indicate similarity in the chemical nature of both the class I and class II MHC antigens expressed by the human HCC cell lines and by a human B lymphoblastoid cell line Raji. Furthermore, a new variant form of class I antigen was detected in some of these HCC cell lines. Immunohistochemical studies of HCC tissues using the peroxidase-antiperoxidase staining method indicated that class I and class II antigens were detectable in 7 out of 11 and 3 out of 11 HCC tissues from patients, respectively. The availability of MHC class I antigen-positive cultured HCC cell lines, including the poorly differentiated lines that also express MHC class II antigen, has provided us with interesting models to study the relationship between expression of MHC antigen and transformation and differentiation of human hepatocytes. These studies will also allow us some insight into the role of MHC class I and class II antigen in the immunosensitivity and immunogenecity of HCC cells to the host-immune response.

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Section: Introductionmentioning

confidence: 99%

Expression of class I and class II major histocompatibility antigens on human hepatocellular carcinoma.

Sung¹,

Hu²,

Hsu³

et al. 1989

J. Clin. Invest.

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“…Fluorescence analyses of the variants HK13.S5 and HK13.S6 with a panel of six monoclonal anti-Kk anti-'bodies and a comparison of the results with reactivity patterns obtained from the previously isolated structural variants HK13.S1, HK13.S3, and HK22.SZ.L1 (11) show identical patterns of HK13.S5 and HK22S2.Ll. The latter variant had been isolated using a different selection protocol from HK22 cells.…”

Section: Discussionmentioning

confidence: 90%

“…Propidium iodide enters only dead cells and accumulates in the nucleus (22). This technique was not applied in the selections described here since the 1.4 x lo4 K t molecules per cell (11). Staining of these viability of HK13 cells was always greater than 90% in the beginning and cells that died during the sort could easily be excluded by scatter gating.…”

Section: Dual Fluorescence Analysis and Sortingmentioning

confidence: 99%

“…The efficiency of the earlier sorts could not be determined and for this reason it is not possible to calculate the frequency of the variants in the wild type population from the number of sorts and the fraction of deflected cells per sort. The frequency of Kk structural variants in the HK13 line has been calculated previously to be 10-5-10-6 per cell and generation (11 Serological Analysis of the Variants HK13.S5 and HK13S6 Clones from both variants were analyzed for binding of six fluoresceinated Kk-specific monoclonal antibodies in the FACS, including the mabs used in the selections. The results are listed in Table 2.…”

Section: Isolation Of Variants Carrying Structurally Altered Kk Molecmentioning

confidence: 99%

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Inexpensive upgrading of a FACS I and isolation of rare somatic variants by double‐fluorescence sorting

Weichel¹,

Liesegang²,

Gehrke³

et al. 1985

Cytometry

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We have modified a FACS I by addition of a tibodies labelled with FITC or Texas Red, we tunable dye laser and an optical system for have isolated from a murine T-cell lymphoma fluorescence detection that allows physically line variant subclones expressing structurally independent measurement of green and red altered histocompatibility class I (H-2Kk) immunofluorescence. These modifications are molecules. inexpensive and should be applicable to most single-laser systems. By using the modified machine and double-fluorescence activated Key words: Dual immunofluorescence, cell selection with H-2Kk-specific monoclonal an-sorting, Texas Red, H-2 variantsThe experiments reported in this paper were aimed at isolating structural variants from the mouse lymphoma line LDHB that express altered instead of wild type H2Kk molecules on the cell surface. These variants are interesting for the investigation of the structural basis of class I antigen function in immune recognition. Furthermore, they can be used to approach the question of which types of somatic mutation occur in the polymorphic family of class I genes.In our previous work, we had achieved this aim by inhibiting the binding of one fluorescent monoclonal anti-Kk antibody to the cells by an excess of a second, unlabelled one and selecting for rare fluorescent cells in the fluorescence activated cell sorter (FACS) (10). This approach was restricted to the selection of structural variants that had lost the expression of one of two Kk determinants, which had to be sufficiently close to each other (topographically) so that the binding of an antibody to one of them would inhibit the binding of a second antibody to the other. In the present work this limitation was overcome by staining wild type cells with two monoclonal anti-Kk antibodies that are labelled with green and red fluorescent tags, respectively, and enriching the cells that carry one label only. For this purpose, we have upgraded a single-laser FACS I instrument by addition of a dye laser that supplies the excitation light for red-fluorescent dyes, such as Texas Red or propidium iodide, that can be used for dual parameter sorting with fluorescein as a green fluorescent label. In contrast to other approaches to double (or triple) fluorescence (161, the dye laser is pumped by the same argon laser that provides the 488 nm light for fluorescein excitation. MATERIALS AND METHODS Cell SorterThe modifications described here were added to a FACS I instrument (Becton Dickinson, Mountain View, CA; serial no. 04). A 5-watt argon ion laser (SpectraPhysics Model 164-08, Darmstadt, FRG) operated at 4 Watts in an all-line mode to give approximately 800 milliwatts at 488 nm and 1.7 watt at 514 nm served as a source for 488 nm excitation of fluorescein and for pumping a Model 375 dye laser (Spectra-Physics, Darmstadt, FRG). The latter was operated with Rhodamin 6G Cambda Physik, Gottingen, FRG) in a setup as described by . Reflectors, dichroic mirrors, and interference and coloured-glass filters used in the system (Fig. 1)

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“…Just as the genotype of neoplastic cells in cultpure is extremely unstable, tumor cells in "vivo probably progress via the sequential activation, mutation, and inactivatipn of a variety of gene products (30)(31)(32). Therefore, any molecular event in a tumor variant that results in the loss of the class I restriction element required for CTL recognition of the tumor cell could provide a selective advantage, leading to c{onpl expai)sion of this variant and, fixation in 'the terminal pheno- 47 Cytolytic nation of class I sequences; transcriptional inactivation; defects in posttranslational processing; or even loss of 132-microglobulin, a small protein associated with class I products on the cell surface (10,(33)(34)(35)(36). Activation or loss of specific transcriptional regulators might also be relevant, although there is, as yet, no molecular description of the factors that might be involved.…”

Section: Molecular Mechanisms Involved In Attenuation Of Class I Exprmentioning

confidence: 99%

Histocompatibility Antigens on Murine Tumors

Goodenow

Vogel

Linsk

1985

Science

156

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Recent advances in tumor immunology suggest that the expression of the histocompatibility antigens, encoded by the major histocompatibility complex, is important in controlling the metastatic growth of certain murine tumors. The anomalous expression of histocompatibility antigens in many neoplasms appears to be associated with the ability of these cells to evade the immune system and progress to metastasis. This review examines some of the underlying molecular and immunobiological interactions that might determine the metastatic outcome of cellular transformation.

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Somatic variation of H-2Kk expression and structure in a T-cell lymphoma: instability, stabilization, high production and structural mutation.

Cited by 11 publications

References 28 publications

Expression of class I and class II major histocompatibility antigens on human hepatocellular carcinoma.

Expression of class I and class II major histocompatibility antigens on human hepatocellular carcinoma.

Inexpensive upgrading of a FACS I and isolation of rare somatic variants by double‐fluorescence sorting

Histocompatibility Antigens on Murine Tumors

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