A cloned H-2 class I gene from a t
w32-derived recombinant t haplotype identified as functional tH-2KtH-2KtH-2K
                q
               gene

The identification of a unique major histocompatibility complex class I gene, designated Q10, which encodes a secreted rather than a cell surface antigen has led to questions regarding its potential role in regulating immunological functions. Since the Q10 gene is specifically activated only in the liver, we sought to define the molecular mechanisms which control its expression in a tissue-specific fashion. Results obtained by transfection of the cloned Q10 gene, either in the absence or presence of a heterologous transcriptional enhancer, into a variety of cell types of different tissue derivations are consistent with the Q10 gene being regulated at two levels. The first is by a cis-dependent mechanism which appears to involve site-specific DNA methylation. The second is by a trans-acting mechanism which would include the possibility of an enhancer binding factor. The ability to efficiently express the Q10 gene in certain transfected cell lines offers an opportunity to obtain this secreted class I antigen in quantities sufficient for functional studies; this should also make it possible to define regulatory sequences which may be responsible for the tissue-specific expression of Q10.

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Functional expression of a heterologous major histocompatibility complex class I gene in transgenic mice

Molecular and Cellular Biology ◽

10.1128/mcb.7.11.4003-4009.1987 ◽

1987 ◽

Vol 7 (11) ◽

pp. 4003-4009

Author(s):

C Bieberich ◽

T Yoshioka ◽

K Tanaka ◽

G Jay ◽

G Scangos

Keyword(s):

Major Histocompatibility Complex ◽

Transgenic Mice ◽

Major Histocompatibility Complex Class ◽

Inbred Mice ◽

Class I ◽

Dependent Manner ◽

Complex Class ◽

Major Histocompatibility ◽

Histocompatibility Complex ◽

I Gene

The regulated expression of major histocompatibility complex class I antigens is essential for assuring proper cellular immune responses. To study H-2 class I gene regulation, we have transferred a foreign class I gene to inbred mice and have previously shown that the heterologous class I gene was expressed in a tissue-dependent manner. In this report, we demonstrate that these mice expressed the transgenic class I molecule on the cell surface without any alteration in the level of endogenous H-2 class I antigens. Skin grafts from transgenic mice were rapidly rejected by mice of the background strain, indicating that the transgenic antigen was expressed in an immunologically functional form. As with endogenous H-2 class I genes, the class I transgene was inducible by interferon treatment and suppressible by human adenovirus 12 transformation. Linkage analysis indicated that the transgene was not closely linked to endogenous class I loci, suggesting that trans-regulation of class I genes can occur for class I genes located outside the major histocompatibility complex.

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Regulated expression of a murine class I gene in transgenic mice

Molecular and Cellular Biology ◽

10.1128/mcb.6.4.1339-1342.1986 ◽

1986 ◽

Vol 6 (4) ◽

pp. 1339-1342

Author(s):

C Bieberich ◽

G Scangos ◽

K Tanaka ◽

G Jay

Keyword(s):

Transgenic Mice ◽

Germ Line ◽

Inbred Mice ◽

Class I ◽

Endogenous Gene ◽

Histocompatibility Complex ◽

Unique System ◽

Regulated Expression ◽

I Gene

The major histocompatibility complex class I genes play an essential role in the immune presentation of aberrant cells. To gain further insight into the regulation of the expression of these class I genes and to better define the functions of their protein products, we made use of the technique of gene transfer into the germ line of inbred mice. With the use of locus-specific DNA probes, we observed that a transgenic class I gene was expressed in a tissue-dependent fashion analogous to that of an endogenous class I gene. In addition, the level of expression of the transgenic gene was substantially higher that that of the endogenous gene. The availability of transgenic mice properly expressing a foreign murine class I gene provides a unique system to further define the role of the class I antigens in the maturation of the immune response and in determining the malignant and metastatic phenotypes of tumor cells.

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Cis- and trans-repression of class I major histocompatibility gene expression in Abelson virus-transformed murine leukemia

Blood ◽

10.1182/blood.v78.2.524.524 ◽

1991 ◽

Vol 78 (2) ◽

pp. 524-532 ◽

Cited By ~ 3

Author(s):

RA Zeff ◽

YF Zhao ◽

R Tatake ◽

H Lachman ◽

F Borriello ◽

...

Keyword(s):

Gene Expression ◽

Cell Line ◽

Mhc Class I ◽

Leukemic Cell ◽

Class I ◽

Leukemic Cell Line ◽

Cis And Trans ◽

I Gene ◽

Murine Leukemia ◽

Mhc Class I Gene

Abstract Numerous tumor cell lines of leukemic origin are known to modulate cell surface expression of major histocompatibility complex (MHC) class I antigens resulting in alterations in their immune detection and tumorigenicity. We have been studying the mechanisms responsible for attenuation of MHC class I gene expression in an H-2 heterozygous (H-2b x H-2d) Abelson-Murine leukemia virus (A-MuLV)-transformed leukemic cell line (designated R8). Here we report that treatment of the R8 cell line with the protein synthesis inhibitor cycloheximide (CHX) increased H-2Kb steady-state messenger RNA (mRNA) levels several fold. The induced H-2Kb mRNA transcripts were functional, as demonstrated by their ability to be translated into immunoprecipitable H-2Kb alloantigen. H-2Kb null variants derived from the R8 cell line were shown to be the product of both cis- and trans-acting mechanisms, insomuch as the treatment of R8-derived H-2Kb non-expressor lines with CHX re-established expression of H-2Kb mRNA to the same extent as transfection of the variant cell line with the wild-type H-2Kb gene. Such findings indicate that downregulation of MHC class I gene expression is constitutive for the R8 leukemic cell line, a phenomenon that may be related to the immature pre-B-cell phenotype of this A-MuLV transformant.

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