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Query: UNIPROT:P06889 (Mol)
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The class I major histocompatibility complex genes are composed of classical and nonclassical genes, the latter being largely nonfunctional. To understand the evolutionary relationships of the two groups of class I genes, a phylogenetic analysis of DNA sequences was conducted using 45 genes from six mammalian and one avian species. The results indicate that nonclassical genes in one species are more closely related to classical genes from the same species than to nonclassical genes from a species belonging to a different order or family. This indicates that the differentiation of classical and nonclassical genes occurs rather rapidly in the genome. Classical genes are apparently duplicated with a high frequency in the evolutionary process, and many of the duplicated genes seem to degenerate into nonclassical genes as a result of deleterious mutation. The nonclassical Qa genes in the mouse have sequences homologous to regulatory sequences involved in the universal expression of classical class I genes, but they have accumulated numerous nucleotide substitutions in these sequences. The pattern of nucleotide substitution in nonclassical genes is different from that in classical genes. In nonclassical genes, the rate of nonsynonymous substitution is higher in the antigen recognition site than in other gene regions, as is true of classical genes. However, unlike the case of classical genes, the nonsynonymous rate does not always exceed the synonymous rate in the antigen recognition site. Nonclassical proteins further differ from classical proteins in having amino acid replacements in conserved antigen recognition site positions. These observations are consistent with the hypothesis that nonclassical genes have originated from classical genes but have lost classical class I function because of deleterious mutation.
Mol Biol Evol 1989 Nov
PMID:Evolution of the major histocompatibility complex: independent origin of nonclassical class I genes in different groups of mammals. 248 36

A region upstream of the murine major histocompatibility complex gene, E alpha d, has been shown previously to be required for B-cell expression. Binding of the B-cell-specific factor, NF-kappa B, to a site within this region is indistinguishable from that observed with the kappa enhancer binding site. NF-kappa B may be responsible for E alpha d B-cell expression.
Mol Cell Biol 1989 Feb
PMID:NF-kappa B binds within a region required for B-cell-specific expression of major histocompatibility complex class II gene E alpha d. 249 3

Expression of major histocompatibility complex antigens by epithelial cells may play a role in the aetiology of autoimmune disorders. We have studied the effect of gamma-interferon on SGHTL-34, a human thyroid cell line which constitutively expresses class I but not class II antigens. gamma-Interferon induced the expression of class II and increased the expression of class I molecules (assessed by flow cytofluorimetry) in a dose-dependent manner. Thyrotrophin or phytohaemagglutinin had no effect on either class I or class II expression. However, a supernatant from phytohaemagglutinin-stimulated peripheral blood mononuclear cells, containing 6400 U gamma-interferon/ml, was an effective inducer of both class I and class II antigens. These data clarify earlier studies using primary thyroid cultures, which are contaminated with cells of the immune system.
J Mol Endocrinol 1989 May
PMID:Immune induction of major histocompatibility complex antigens on a human thyroid cell line (SGHTL-34). 250 34

We develop and apply a new method for estimating the locations of hypervariable residues in immunoglobulin-related molecules. The method differs from the standard introduced by Wu and Kabat in two essential ways: (1) we take explicit account of the type of substitution at a given position, rather than just the total number of substitutions, and (2) we use an explicit statistical decision criterion for classifying a site into either the complementarity determining or framework category. Simulations indicate that the method is reliable with relatively little data, approximately 5% of the sites being misclassified when 10 sequences are aligned. The method is applied to immunoglobulin light chains and to class 1 and class 2 products of the major histocompatibility complex.
Mol Immunol 1989 Dec
PMID:Identifying weak signals in the presence of noise: a new method of locating potential ligand contact residues in immunoglobulin-related molecules. 251 15

Human adenoviruses are providing insights into strategies that viruses may adopt to evade immune surveillance. There are 47 serotypes that form six groups (A to F) with different genetic and biological properties. Adenovirus type 2 (Ad2) and Ad5, two group C types, the most common and best understood in terms of molecular biology, cause respiratory infections in young children and often form persistent infections. Following infection, the linear duplex DNA genome is expressed in two broad phases: "early", when viral proteins function to usurp the cell; and "late", when viral DNA and structural proteins are synthesized and virions are assembled. One of the early transcription units, region E3, encodes two proteins that appear to counteract different branches of the host's anti-viral defenses. A 19,000 Mr protein called gp19K protects cells against cytolysis by adenovirus-specific cytotoxic T lymphocytes (CTL). Gp19K has two properties that are crucial to this function: it is localized in the endoplasmic reticulum, and it binds strongly to class I antigens of the major histocompatibility complex (MHC). The effect of these two properties is to block transport of class I antigens to the cell surface. In order to lyse adenovirus-infected cells, CTL must recognize adenovirus peptide antigens complexed with class I major histocompatability complex antigens displayed on the cell surface. Since gp19K prevents this, it renders the cell effectively invisible to CTL. The second anti-immune E3 protein is a 14,700 Mr protein called 14.7K. The 14.7K protects adenovirus-infected cells against cytolysis by tumor necrosis factor (TNF). TNF is a pleiotropic immunoregulatory protein that has anti-viral properties and is believed to provide a defense against virus infections. The 14.7K presumably counteracts the anti-viral effects of TNF in vivo. The mechanism of action of the 14.7K is unknown. Further studies on gp19K and 14.7K should assist our understanding of the immune system and adenovirus pathogenesis.
Mol Biol Med 1989 Oct
PMID:Adenovirus region E3 proteins that prevent cytolysis by cytotoxic T cells and tumor necrosis factor. 253 58

The promoter regions of class II major histocompatibility complex genes contain two highly conserved sequences, the X and Y boxes, which may be involved in the control of class II gene expression. In this study, we correlate in vivo functional assays for cis-acting regulatory elements in the HLA-DR alpha gene with in vitro binding assays for trans-acting regulatory proteins. Mutagenesis and transient transfection analyses indicated that both the X and Y boxes were important for HLA-DR alpha promoter function in a B lymphoblastoid cell line. Although specific nuclear protein interactions with the X consensus sequence were not apparent, the Y box, which contained an inverted CCAAT sequence, did bind specifically to at least one nuclear protein. This Y box-binding protein was present in nuclear extracts of all cell types examined, including human B and T cells and HeLa cells. The molecular mass of the protein, as determined by photoactivated protein-DNA cross-linking, was approximately 40 to 50 kilodaltons. Mutagenesis of the Y box that decreased protein binding also decreased promoter activity, implying that protein binding to this DNA sequence is important for DR alpha promoter function.
Mol Cell Biol 1989 Jan
PMID:Class II box consensus sequences in the HLA-DR alpha gene: transcriptional function and interaction with nuclear proteins. 253 24

We have determined the DNA sequence of a BALB/c Tla region class I gene from the major histocompatibility complex (MHC) that had been identified previously as encoding a murine antigen by DNA-mediated gene transfer. Analysis of the DNA sequence shows, however, that this gene, the T1c gene from the Tlac genotype, could not encode a TL antigen or any other functional class I molecule due to the presence of numerous stop codons and frameshift mutations in the coding regions. This result suggests that the earlier transformation data may have been incorrect or perhaps that the clone containing the T1c gene contains sequences that induced expression of a serologically reactive Tla gene in the genome of the recipient L cell. The T1c gene is structurally related to the previously sequenced T13c gene that encodes a serologically defined TL antigen. The 3' half of the T1c gene including exons 4, 5, 6, and the 3' untranslated region has about 85% nucleotide similarity (including introns) with the corresponding parts of the T13c gene; however, the 5' half of the T1c gene has little homology with the T13c gene. There is a sharp line of demarcation between the homologous and nonhomologous regions, and this border occurs precisely at a B2 Alu repeat sequence present in the T13c gene. This suggests that a recombination event took place here and that an Alu repeat sequence that is known to have characteristics of transposable elements played some role in a recombination or gene conversion event.
J Mol Evol 1989 Apr
PMID:DNA sequence of a class I pseudogene from the Tla region of the murine MHC: recombination at a B2 alu repetitive sequence. 254 31

B lymphocytes are very efficient antigen-presenting cells when they bear surface receptors for the antigen in question. However, there is very little known about the intracellular events occurring between the time B cells bind native antigen and present it in processed form to T cells. To analyze internalization and degradation of antigen versus anti-Ig or anti-MHC antibodies by B cells, we have used highly purified resting antigen-specific B lymphocytes that bind the hapten, trinitrophenyl. These cells were treated with [125I]-labeled trinitrophenylated antigens or with [125I]-labeled antibodies reactive with either cell surface immunoglobulin or major histocompatibility complex (MHC) (class I or class II) molecules. The fate of these proteins was followed by measuring the amount of acid soluble and insoluble radioactivity associated with the cells or released into the incubation medium. The cell-associated and released radioactivity was further analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Our results demonstrate that the kinetics of degradation of specific antigen into acid soluble fragments which are released into the culture medium closely parallel those with which B cells acquire the ability to specifically conjugate to carrier-specific T cells. In contrast, degradation of anti-Ig is more complete than the degradation of antigen but requires a longer period of time to reach completion. Furthermore, the initial release of soluble fragments of anti-Ig as compared to antigen into the culture medium is marginally slower. Finally, there is significant intracellular accumulation of degradation intermediates when anti-Ig is processed, but this is not the case with antigen.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Immunol 1989
PMID:The processing of antigen and anti-Ig by antigen-specific B cells. 261 Aug 53

By varying growth conditions, we identified a novel mechanism of autocrine regulation of major histocompatibility complex (MHC) class I gene expression by induction of beta interferon gene expression in transformed BALB/c-3T3 cells. Low-serum conditions enhanced MHC class I antigen expression in v-rasKi- and v-mos-transformed BALB/c-3T3 cells but not in untransformed BALB/c-3T3 cells. Transformed and untransformed cells grown under standard serum conditions (10% bovine calf serum) expressed similar cell surface levels of MHC class I antigens. However, low-serum conditions (0.5% bovine calf serum) induced four- to ninefold increases in cell surface levels of MHC class I antigens in both v-rasKi- and v-mos-transformed cells but not in untransformed cells. These increases in MHC class I gene expression were seen at both the mRNA and cell surface protein levels and involved not only the heavy-chain component of the class I antigens but also beta 2 microglobulin. Beta 1 interferon mRNA and beta interferon-inducible 2',5'-oligoadenylate synthetase mRNA were induced by growth under low-serum conditions in transformed BALB/c-3T3 cells, and antibodies to beta interferon blocked the induction of MHC class I antigen expression by serum deprivation in these cells. These results demonstrate that growth under low-serum conditions leads to induction of beta interferon expression in oncogene-transformed cells which then directly mediates autocrine enhancement of MHC class I gene expression.
Mol Cell Biol 1989 May
PMID:Autocrine induction of major histocompatibility complex class I antigen expression results from induction of beta interferon in oncogene-transformed BALB/c-3T3 cells. 266 64

A new retrovirus vector containing the gene for hygromycin B resistance (hyg) as a selectable marker under the control of an internal simian virus 40 promoter was constructed. It was used, together with an analogous previously described vector, DO1, which contains the gene for G418 resistance, to introduce and express the genes for the two chains of a human class II major histocompatibility complex antigen in NIH 3T3 cells. In addition, these vectors were used to express DR antigens in two human mutant B-lymphoblastoid cell lines, one of which was deleted for both alleles of the DR alpha gene and the other of which expressed no class II antigens because of a genetic defect in a putative trans-acting regulatory factor.
Mol Cell Biol 1987 Nov
PMID:Expression of HLA-DR antigen in human class II mutant B-cell lines by double infection with retrovirus vectors. 282 20


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