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Query: UNIPROT:P06889 (Mol)
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The class II region of the major histocompatibility complex (Smh) in the mole rat, Spalax ehrenbergi, consists of only two gene families, P and Q, instead of the four families (P, O, Q, and R) found in all other mammals studied to date. The Spalax P family consists of at least four beta and three alpha genes or gene fragments. In DNA-hybridization experiments, two of the beta genes behave as bona fide P-family members in that they hybridize strongly with human DP beta probes and hybridize weakly with probes specific for other class II gene families. The other two beta genes, on the other hand, hybridize weakly with human DP beta probes and nearly as well with human DQ beta probes. To determine the evolutionary relationships among these P-like genes, we have sequenced one of them. The sequence reveals, on the basis of its organization, that the gene clearly belongs to the P family, yet, on the basis of its nucleotide sequence, it is only slightly more similar to human DP than to human DQ genes. These results indicate that in the Spalax the P family of genes split into two subfamilies, PA and PB. For unknown reasons, one of these subfamilies (PB) retained more similarity to the Q gene family than did the other (PA).
Mol Biol Evol 1987 May
PMID:Evolutionary diversification of class II P loci in the Mhc of the mole-rat Spalax ehrenbergi. 283 71

Two synthetic peptides from different regions of the glycoprotein D of herpes simplex virus (HSV) have been used to determine whether or not anti-peptide IgG responses can be generated in the absence of adjuvant. Based on an earlier demonstration (Carayanniotis and Barber, 1987) that protein antigens could be made immunogenic in the absence of adjuvant, if coupled to MAbs specific for the recipient's class II major histocompatibility complex (MHC) antigens, the HSV synthetic peptides were photocoupled to avidin and mixed with biotinylated anti-class II or control antibodies. Peptide-specific IgG responses were obtained when avidin-peptide conjugates coupled to an anti-I-Ak MAb were injected into (H-2k x H-2b) F1 mice, but not when injected into H-2b mice. The same avidin-peptide conjugates were non-immunogenic when coupled to a control anti-influenza virus nucleoprotein antibody or biotinylated bovine serum albumin. These data indicate that targeting synthetic peptides to class II bearing cells in vivo can elicit peptide-specific IgG responses without the need for adjuvant. These findings offer a new approach to the design and delivery of adjuvant-independent vaccine agents based on synthetic peptide antigens.
Mol Immunol 1988 Sep
PMID:Delivery of synthetic peptides by anti-class II MHC monoclonal antibodies induces specific adjuvant-free IgG responses in vivo. 285 Apr 98

Tumor necrosis factor (TNF) dramatically alters the levels of various surface components of the blood vessel wall, such as blood coagulation enzyme receptors, leukocyte-adhesive receptors, and class 1 major histocompatibility complex antigens, which may have relevance to its effects in septic shock, angiogenesis, and tumor growth. However, the precise mechanism by which the cytokine is able to accomplish this remodeling of the endothelial cell surface has not been defined. We have demonstrated that exposure of bovine and human endothelial cells to TNF leads to suppression of the functional cell surface thrombin receptor, thrombomodulin (TM), and TM mRNA of virtually identical magnitude. The cytokine has no significant effect on the stability of TM mRNA or endothelial receptor turnover. Nuclear run-on studies reveal that the treatment of endothelial cells with TNF for short periods reduces TM gene transcription to as little as 3% of control values and that this inhibition does not require new protein synthesis.
Mol Cell Biol 1988 Dec
PMID:Tumor necrosis factor suppresses transcription of the thrombomodulin gene in endothelial cells. 285 3

Regulation of T cell effector functions by major histocompatibility complex (MHC) gene products has been extensively researched. Investigations in this area have established several important concepts of immunobiology. First, genes within the I-region of the MHC profoundly affect development of immune responses through their effects on cell-cell interactions. In the course of analyzing antigen-induced T cell activation, investigators identified specific Ir-genes by demonstrating that certain strains of mice were unable to develop immunity to defined antigens. It is now accepted that immune response defects in murine species are potentiated by cell surface molecules encoded within the I-subregion of the MHC, called Ia. Those molecules coded within the I-A subregion have the potential to be expressed by many different cell types. Second, induction of helper T cell effector function requires recognition of antigen in association with I-region encoded, cell surface molecules. For example, only a single structural combination of antigenic determinant and Ia molecule can deliver the inductive signal(s) to potential helper T cells. This fundamental aspect of helper T cell activation, now documented in numerous experimental systems, is referred to as MHC- or I-region restricted, antigen recognition. MHC-restriction is a characteristic of T cells mediating delayed-type hypersensitivity, help, and cytotoxicity. Third, several lines of evidence have established that T cell recognition of self-MHC molecules is a modifiable phenotype; conferred by a receptor having both variable and constant regions and not encoded by genes in the MHC. The development of both thymic grafted homozygous nu/nu mice and irradiation-induced bone marrow chimeras as experimental models resulted in a better understanding of the mechanism of MHC-restricted, antigen recognition. It was observed that expression of MHC gene products by the host is sufficient to select a new immune response phenotype for cellular interactions. The selection process takes place during T cell maturation, in the absence of antigen and under the dominant influence of the thymus, even though there is ample evidence for selective pressure in the extrathymic environment. For example, the self-MHC recognition repertoire of T cells in P----F1 chimeras undergoes an initial expansion which results in an F1 immune response phenotype. This expansion is followed by an apparent contraction back to the immune response phenotype of the parental donor. The contraction is time dependent and reflects accessory cell turnover in the irradiated host.(ABSTRACT TRUNCATED AT 400 WORDS)
J Mol Cell Immunol 1986
PMID:Ontogeny of MHC-linked, T cell-mediated suppression is regulated by the T cell genotype. 285 3

Human chromosome 6 encodes both the interferon gamma receptor as well as the class I major histocompatibility complex antigens, HLA-A, -B, and -C. However, the presence of chromosome 6 in somatic cell hybrids is insufficient to confer sensitivity to human interferon gamma (Hu-IFN-gamma) as assayed by class I HLA induction; it is necessary for both human chromosomes 6 and 21 to reside in the hybrid to generate a response to Hu-IFN-gamma. Treatment of such a hamster-human hybrid, Q72-18, with Hu-IFN-gamma induces the class I HLA antigens. Q72-18 cells selected by fluorescence-activated cell sorting for the loss of class I HLA induction also lost human chromosome 21. Fusions of such cells to a hybrid that contains only human chromosome 21 reconstitutes HLA antigen induction by Hu-IFN-gamma. Furthermore, fusions of hybrids containing a translocated human chromosome 6q and the HLA-B7 gene to a line containing only human chromosome 21 or a translocated 21q also reconstitutes HLA-B7 mRNA and antigen induction by Hu-IFN-gamma. Thus the segregation of cells on the basis of a biological effect by fluorescence-activated cell sorting and reconstitution by hybrid fusion provides a strategy by which some biological pathways can be mapped at a chromosomal level.
Somat Cell Mol Genet 1988 Nov
PMID:Chromosome mapping of biological pathways by fluorescence-activated cell sorting and cell fusion: human interferon gamma receptor as a model system. 297 62

The ability to distinguish self and non-self remains a central, though incompletely understood, prescript of immunology. In the absence of disease, the organism maintains immunological unresponsiveness, or tolerance, to self proteins. Unresponsiveness also extends to certain exogenous proteins, and unresponsiveness to many of these proteins is regulated by immune response (Ir) genes encoded by the major histocompatibility complex (MHC). It has been suspected by many that there is a fundamental association between the principles that govern immunological self-tolerance and experimentally observed Ir gene control of responses to exogenous antigens. Does MHC-linked unresponsiveness to a particular antigen result from cross-reactivity between the exogenous antigen in question and self at some critical level(s)? We have approached this question through the study of in vitro antibody responses to variants of insulin. The amino acid sequence of insulin is highly conserved and murine antibody responses to heterologous insulins are controlled by H-2 linked Ir genes. We have previously demonstrated that although pork insulin fails to stimulate antibody responses in nonresponder C57BL/10 mice, it does prime helper T (Th) cells that support secondary antibody responses to pork insulin. However, dominant, pork insulin-primed suppressor T (Ts) cells normally mask this helper T cell activity. Thus, nonresponsiveness to pork insulin is controlled by highly specific suppressor T cells that prevent the expression of function, but not the priming of helper T cells. Here, we extend these studies to demonstrate that T cells from nonresponder C57BL/10 mice immunized with pork insulin have primed helper T cells and dominant suppressor T cells that cross-react with autologous insulin.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Immunol 1985
PMID:Stimulation of helper T cells and dominant suppressor T cells that recognize autologous insulin. 297 25

Helper T lymphocytes recognize foreign antigen together with class II major histocompatibility complex (Mhc) molecules on the surface of antigen-presenting cells (APC). However, it is not known in what form soluble protein antigens are presented to T cells. The difficulty of serologically demonstrating the presence of soluble antigen on the surface of APC, the observed rapid degradation of antigen by these cells, and the finding that under special circumstances peptides of a certain protein are more antigenic that the whole molecule have led to the notion that foreign antigens must be rendered immunogenic for helper T cells by internalization, processing (probably involving enzymatic fragmentation), and redisplay on the membrane of APC in association with class II Mhc molecules. To analyze antigen recognition by helper T cells and to assess the biological significance of antigen processing, we have constructed liposomes that carry inserted class II Mhc molecules and a protein antigen coupled covalently to one of the lipid constituents of the artificial membrane. We demonstrate here that such liposomes are capable of inducing proliferative responses of long-term cultured T-cell clones, and interleukin-2 (Il-2) production by a T-cell hybridoma in an antigen-specific, Mhc-restricted fashion, in the absence of antigen-presenting cells. The responses require the presence of foreign antigen and class II molecules on the same lipid vesicles. The magnitude of responses is critically dependent on the lipid composition, the density of bound antigen, and the concentration of liposomes in cell cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Immunol 1986
PMID:Major histocompatibility complex-restricted and unrestricted activation of helper T cell lines by liposome-bound antigens. 297 28

Mechanisms underlying major histocompatibility complex (MHC)-linked immune response (Ir) gene regulation of immune responses have been the subject of considerable interest and debate in recent years. Two general mechanisms have been proposed to account for antigen-specific, Ir gene-mediated unresponsiveness. In one, defective antigen presentation resulted from the failure of processed nominal antigen and Ia antigen to associate on the antigen presenting cell membrane in a manner sufficient for helper T cell (Th cell) activation. By contrast, it has been proposed that selected Th cell clones were deleted from the repertoire during ontogeny or otherwise rendered unresponsive to the antigen-Ia complex, i.e., functionally deleted. Either of these mechanisms would account for the deficient activation of antigen-specific, Th cells observed in genetic low or nonresponder mice. In addition, the failure of mice to respond to certain antigens under Ir gene control has been attributed to the activation of specific suppressor T (Ts) cells. The latter mechanism might be considered a corollary or subset of the clonal deletion model. However, an important distinction exists. In the case of active, Ts cell-mediated Ir gene regulation, genetic low responder animals should retain the capacity for antigen-induced activation of Th cells, or Th cell activity should be demonstrable in these mice. In this communication, experiments are described which are designed to evaluate the possibility that active Ts cell-mediated regulatory mechanisms were of general importance in mediating Ir gene-related unresponsiveness.(ABSTRACT TRUNCATED AT 250 WORDS)
J Mol Cell Immunol 1987
PMID:The role of suppressor T cells in the expression of immune response gene function. 297 44

The S region of the murine major histocompatibility complex contains two closely related genes: C4, encoding the fourth component of complement, and Slp, encoding sex-limited protein. We cloned these genes from a cosmid library of the B10.W7R strain that does not show androgen regulation of the Slp protein. Restriction site polymorphisms revealed at least four C4-like genes within the Sw7 locus, indicating evolutionary amplification of this region. Transfection of these genes into L cells resulted in expression, processing, and secretion of immunologically correct C4 and Slp proteins. At least two different Slp genes and one C4 gene were capable, after transfection, of expressing C4 and Slp indistinguishable from macrophage-derived protein. A third Slp gene exists within this locus whose recombinant cognate did not express in L cells. Thus, the B10.W7R S region includes one C4 gene and at least three Slp-like genes.
Mol Cell Biol 1986 Jan
PMID:Multiple C4/Slp genes distinguished by expression after transfection. 302 18

DNA methylation of two murine major histocompatibility complex (H-2) class I genes was examined in hybridizations to MspI and HpaII chromosomal DNA restriction digests. Q10, which exhibits liver-specific expression, and H-2Kb, a transplantation antigen gene, were examined in liver, spleen, thymus, and cell-line DNAs. Unmethylated Q10 gene sequences were detected only in the liver, whereas the H-2Kb gene was unmethylated in all tissues examined.
Mol Cell Biol 1986 Jan
PMID:Liver-specific expression of a Qa-encoded class I gene is associated with DNA hypomethylation. 302 31


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