Disease relevance of H2-K1

• Regulated expression of an introduced MHC H-2K bm1 gene in murine embryonal carcinoma cells [1].
• Furthermore, CD4(+) T cells from CD1d(-/-) knockout (KO) B6 donor mice but not those from MHC-I(-/-) (homozygous transgenic mice deficient for beta(2)-microglobulin) KO B6 mice induced a colitis in RAG(-/-) hosts [2].
• Recently, we reported the down-regulation of MHC class I (MHC-I) products in invading tumor cells in human and mouse GL261 gliomas [3].
• Divergent effects of H-2K and H-2D genes on sensitivity of BL6 melanoma cells to NK cells or TNF-mediated cytotoxicity [4].
• In a series of newly isolated AKR leukemias, some tumors expressed large amounts of both H-2K and H-2D molecules, while others had reduced levels of both antigens [5].

Psychiatry related information on H2-K1

• We show that in primary spontaneous AKR leukemias, in spite of large individual differences, the expression of high amounts of MuLV gp70 is not random, but is associated with high expression of H-2K and H-2D antigens [6].

High impact information on H2-K1

• Thus, this study characterizes the naturally occurring peptide moiety of an MHC-I/peptide complex recognized by alloreactive CD8+ T cells [7].
• At the centromeric end the t12 lethal maps between TL and H-2D in the Qa region, and distally the tw5 lethal is inseparable from H-2K [8].
• Our previous studies indicate that the Q10 gene is a potential donor gene for the generation of mutations at the H-2K locus by inter-gene transfer of genetic information [9].
• Our findings suggest that the two sequences are derived from allelic class I genes, which are nonpolymorphic, in contrast to H-2K allelic sequences from the same mice, and they may encode liver-specific polypeptides of unknown function [9].
• The hybrid H-2 K antigens were examined for their ability to function as restricting elements for cytotoxic T lymphocytes during influenza A infection [10].

Chemical compound and disease context of H2-K1

• The m144 glycoprotein, expressed by murine cytomegalovirus, is thought to be an MHC-I homolog whose expression prolongs viral survival in vivo by preventing natural killer cell activation [11].
• The effect of indomethacin (INDO), a specific inhibitor of prostaglandin (PG) synthesis, on the expression of markers during thymocyte differentiation such as Thy-1, H-2K, and peanut agglutinin (PNA) receptor was examined by immunofluorescence, using poorly differentiated thymoma, EL-4, as the indicator cells [12].
• The ability of cyclosporine to prevent the increase in Ia and H-2K expression that occurs in mice with graft-vs-host disease (GVHD) was examined by means of absorption, indirect immunofluorescent staining (IIF), and indirect immunoperoxidase staining (IIP) [13].

Biological context of H2-K1

• The transplantation antigens H-2K, H-2D and H-2L are developmentally regulated, highly polymorphic cell surface proteins encoded by the major histocompatibility gene complex (MHC) [1].
• One, Idd-1s, is tightly linked to the H-2K locus on chromosome 17; another, Idd-2s, is localized proximal to the Thy-1/Alp-1 cluster on chromosome 9 [14].
• All CTL lines appear to be restricted in target cell recognition to either the H-2K or the H-2D end of the appropriate H-2 haplotype [15].
• These findings confirm at the clonal level previous observations on the H-2K/D restriction of virus-specific CTL and also demonstrate heterogeneity among H-2 restricted CTL both from the standpoint of viral antigen recognition and cell surface phenotype [15].
• We have searched for expressed genes in 170 kb of cosmid cloned DNA from the H-2K region of the mouse MHC [16].

Anatomical context of H2-K1

• Helper effect could be obtained only toward B cell sources that shared the H-2K and I-A antigens with the hybridoma cells [17].
• KbDb -/- mice have greatly reduced numbers of mature CD8+ T cells, indicating that selection of the vast majority (>90%) of CD8+ T cells cannot be compensated for by beta2-microglobulin-associated molecules other than classical H-2K and D locus products [18].
• NK cells maintain self-tolerance through expression of inhibitory receptors that bind MHC class I (MHC-I) molecules [19].
• We show that line 1, a murine lung carcinoma cell line, has low levels of class I Ag (H-2K, D, and L) because it is deficient in both class I and beta 2-microglobulin (B2M) RNA, and that these mRNA can be coordinately induced with DMSO [20].
• Helper cells activated by allogeneic H-2K or H-2D differences have a Ly phenotype distinct from those responsive to I differences [21].

Associations of H2-K1 with chemical compounds

• The type I endoplasmic reticulum (ER) glycoprotein tapasin (Tpn) is essential for loading of major histocompatibility complex class I (MHC-I) molecules with an optimal spectrum of antigenic peptides and for stable expression of the heterodimeric, polytopic TAP peptide transporter [22].
• Drug treatment does not change cell surface I-A expression, and H-2K levels are apparently decreased one-third by deoxynojirimycin but are not affected by swainsonine [23].
• Using mutant RMA-S cells, it was found that both Brefeldin A (BFA) and chloroquine, but not leupeptin, inhibited MHC-I upregulation response to both peptide and beta 2-m. In contrast to chloroquine, BFA also gave a reduction of background membrane MHC-I expression, presumably due to a block in Golgi transport [24].
• Regulation of T-cell-mediated lympholysis by the murine major histocompatibility complex. II. Control of cytotoxic responses to trinitrophenyl-K and -D self products by H-2K- and H-2D-Region genes [25].
• Adsorption experiments showed that the only cells capable of adsorbing the suppressor factor are DNFB-immune T cells from donors which share with the factor-producing strain either the H-2K or H-2D locus [26].

Physical interactions of H2-K1

• We obtained mice deficient for major histocompatibility complex (MHC) molecules encoded by the H-2K and H-2D genes [18].
• We have recently shown that the MHC-I ligand-binding capacity of the Ly49A NK cell receptor is controlled by the NK cells' own MHC-I [27].
• Peptides eluted from Q10 displayed a binding motif typical of H-2K, D, and L ligands [28].

Regulatory relationships of H2-K1

• Establishment of T-cell clones recognizing difference in H-2K antigen and inducing graft-versus-host disease [29].
• Comparison of H-2 antigens immunoprecipitated from normal spleen cells and from thioglycollate-induced adherent peritoneal exudate cells cultured in the presence or absence of supernatant fluids from concanavalin A-stimulated spleen cells revealed that H-2K' was not expressed on the adherent peritoneal cells [30].
• These spleen cells displayed strong lysis on TNP-modified H-2D end-matched (Kd-Dk) targets as well as enhanced cytotoxicity against H-2 matched (Kk-Dk) or H-2K end-matched (Kk-Dd) target cells [31].
• Transfection of non-expressor cells by v-fos or c-fos genes induces the transcription of H-2K mRNA and elevates the levels of H-2 proteins, but not of other gene products [32].

Other interactions of H2-K1

• However, beta2m associates with a number of MHC-I-like proteins, including HFE [33].
• In crosses of F/St with AKR, the high-virus phenotype of F/St was found to be recessive and was shown to be governed by a single locus, Cxv-1, less than 2 centimorgans from H-2K [34].
• The basic relationship of H-2 K, D, L antigens is revealed also by the shared antigenic specificities between these H-2 molecules which we demonstrate using anti-H-2.28 sera [35].
• TNF-alpha consistently up-regulates the expression of ICAM-1, but not H-2K, in a time- and dose-dependent manner [36].
• IL-10 slightly but reproducibly inhibits the expression of ICAM-1, but not H-2K, in a time- and dose-dependent manner [36].

Analytical, diagnostic and therapeutic context of H2-K1

• The mouse major transplantation antigens H-2K, H-2D and H-2L are highly polymorphic cell-surface glycoproteins which may serve as recognition elements in cell-cell interactions [37].
• Northern blot analysis and isolation of clones from 5.5 and 10.5-day embryo cDNA libraries showed five additional genes encoded in the H-2K region [16].
• To verify that the drug protocol used was capable of altering the glycoconjugates of membrane-associated proteins, the endo-beta-N-acetylglucosaminidase H (endo H)-sensitivity of immunopurified H-2K and I-A was analyzed by SDS-PAGE [23].
• EXPERIMENTAL DESIGN: MHC-I molecule expression on GL261 cells was analyzed in vitro and in vivo by flow cytometry and immunohistochemistry, respectively [3].
• Here, we tested the hypothesis that whole-brain radiotherapy (WBRT) up-regulates MHC-I expression on GL261 tumors and enhances the effectiveness of immunotherapy [3].

References