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Query: UNIPROT:Q00604 (X-linked)
 16,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new polymorphic alloantigen system controlled by loci on the X-chromosome has been identified by using antisera from F1 hybrid mice differing in their X-chromosome. These alloantigens are associated with the X-chromosome. These alloantigens are associated with the X-linked immune response genes controlling the immune response to the so-called "thymus independent antigens" such as type III pneumococcal polysaccharide, poly(I)-poly(C), and denatured DNA. They also show association with the histocompatibility locus present on the X-chromosome. They were mainly detected on a not yet characterized thymus-derived lymphocyte subpopulation. A certain similarity with the major histocompatibility complex of the mouse supports the possibility of additional I-like regions besides the I region of the histocompatibility-2 complex.
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PMID:Lymphocytes alloantigens associated with X-chromosome-linked immune response genes. 26 35

This report has examined the mechanisms by which major histocompatibility complex (MHC) non-restricted suppressor T cells (Ts), induced by the i.v. injection of 2,4-dinitropheny (DNP)-modified, syngeneic lymphoid cells (DNP-LC), suppress the passive transfer of contact sensitivity mediated by syngeneic and allogeneic immune delayed hypersensitivity T cells (TDH). In terms of suppression of syngeneic TDH, it was found that the suppressive action of the Ts was only blocked by pretreatment with soluble syngeneic DNP-LC membrane preparations. Monomeric DNP-lysine, polymeric DNP-protein conjugates, and syngeneic TNP-LC membranes did not inhibit Ts function. Further experiments showed that inhibition of syngeneic suppression could be achieved by DNP-modified-membrane preparations that were only H-2D-region compatible with the Ts donor. Thus, Ts antigen receptors in this system specifically recognize DNP-modified H-2D-region determinants. In contrast, it was found that pretreatment os syninduced Ts with syngeneic DNP-LC membranes did not inhibit the ability to suppress allogeneic TDH. However, pretreatment of Ts with DNP-allogeneic membranes which were H-2D-end compatible to the allogeneic target TDH eliminated their ability to suppress the specific allogeneic TDH, leaving intact suppression of syngeneic or third party TDH. It is proposed that perturbation of the immune system by i.v. injection of syngeneic NDP-LC leads to the induction of a polyclonal wave of DNP-specific Ts activity. Some members of this set of Ts recognize DNP-self MHC determinants with moderate affinity and are thus specifically inhibited after pretreatment with those DNP-self determinants. Other members of this set display receptors which cross-react with high affinity with DNP-allogeneic determinants and thus suppress allogeneic TDH cells. These allosuppressive clones can thus be specifically inhibited only by pretreatment with DNP-LC membranes, MHC-compatible with the target TDH. The data are discussed in terms of current models of T-cell cross-reactivity and T-cell-receptor recognition.
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PMID:Suppressor T-cell mechanisms in contact sensitivity. III. Apparent non-major histocompatibility complex restriction is a result of multiple sets of major histocompatibility complex-specific suppressor T cells induced by syngeneic 2,4-dinitrophenyl-modified lymphoid cells. 31 89

Interest in immunogenetics originated from two streams: (a) histocompatibility in mouse and man, and (b) inheritance of specific immune responses in the guinea pig and mouse. In the mouse, there are genes associated with the major histocompatibility complex (MHC) which (i) code for antigens determining allograft responses and mixed lymphocyte reactions, (ii) control responses to certain antigens (Ir genes), and (iii) code for cell-surface antigens which elicit specific antisera (anti-Ia). In man, there is genetic control, in part X-linked, over levels of immunoglobulins and immunoglobulin classes. Evidence for MHC-linked genetic control is derived from immune responses to (i) micro-organisms, (ii) pollen antigens, (iii) food antigens, (iv) vaccines, (v) inocuous test antigens, and (vi) autoantigens. Some evidence exists for allotype-linked genetic control. Practical aspects concern influences of the MHC on susceptibility to disease, within individuals and populations.
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PMID:Genetic control of immune responsiveness in man. 84 60

Lymphocytes from patients with Wiskott-Aldrich syndrome (WAS) were studied with prometaphase G banding to search for minor chromosome anomalies and in mutagen stress assays to assess the extent of chromosome breakage under these conditions. One patient, a sporadic case of WAS, was found to have a stable inversion of a large segment of one chromosome 6 that involved the region encoding the major histocompatibility complex (MHC). The anomaly was not present in the patient's parents, nor in three other unrelated patients with WAS, all of whom demonstrated X-linked inheritance (based on family history). None of the four patients showed an excessive number of breaks or radial exchange figures following exposure to mitomycin C or diepoxybutane. Thus chromosome fragility in WAS was not confirmed by these studies. However, the incidental finding of 6p inversion in a sporadic case of WAS suggests that genetic rearrangement involving the MHC can result in clinical immunodeficiency mimicking WAS.
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PMID:Cytogenetic studies in Wiskott-Aldrich syndrome: identification of a case with a 6p chromosome abnormality. 395 75

Inbred SJL/J and A.SW/SnJ mice have been bred to produce (SJL female X A.SW male)F1 and A.SW female X SJL male)F1 mice. F1 mice were then crossed to produce (SJL female X A.SW male)F2 and (A.SW female X SJL male)F2 mice. The inbred, F1, and F2 populations were followed for 2 years to determine the incidences of spontaneous reticulum and sarcoma (RCS) expression. SJL mice had a greater than 90% incidence of RCS, although F1 mice showed almost no RCS. The incidence of RCS in the F2 populations was 24.1%. These data were consistent with the hypothesis that in F1 and F2 populations a single dominant A.SW gene is able to suppress the expression of the pleomorphic RCS disease characteristic of the SJL mouse. This gene was not an H-2 gene, since the two strains were congenic with respect to the major histocompatibility complex; this gene was not on the Y-chromosome, and its phenotypic expression was not inherited in an X-linked manner.
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PMID:Single-gene abrogation of spontaneous pleomorphic SJL/J mouse reticulum cell sarcoma expression. 635 30

Immune response (Ir) genes are encoded for by the I region of the major histocompatibility complex (MHC). A class of serologically defined specificities, Ia antigens, is also encoded for by genes within this region. A new Ia specificity, Ia.W39, has recently been defined. It is private for I-Ab and its expression is controlled by a gene on the X-chromosome. Using different approaches, the role of Ia.W39 in the immune response of H-2b mice to beef insulin was examined in a macrophage-dependent T cell proliferation assay. It was found that beef insulin-related Ir gene function was associated with the expression of Ia.W39 by antigen-presenting macrophages and that control of this Ir gene function was X-linked (xid gene).
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PMID:The xid gene controls Ia.W39-associated immune response gene function. 678 86

The CBA/N mouse carries the X-linked immunodeficiency xid, resulting in defective B cell development. B cells from these animals cannot mount antibody responses to type 2 T-independent antigens, and do not synthesize DNA when stimulated with anti-immunoglobulin (Ig) antibodies which are mitogenic for normal B cells. The primary antibody responses of CBA/N mice to T-dependent antigens have also been reported to be abnormal. Here we describe the results of experiments which demonstrate that the B cells from these animals respond abnormally to ligation of CD40, a B cell surface molecule now known to play a key role during T cell-B cell interactions, via its interaction with the counterligand (CD40L) expressed by activated T cells. Hence, xid B cells fail to proliferate when cultured with preactivated T helper type 2 (Th2)T cells (known to express CD40L), with a soluble CD40L-CD8 fusion protein, or in response to monoclonal antibodies to CD40, even in the presence of IL-4 and/or anti-Ig reagents. However, xid B cells do receive abortive activation signals following ligation of CD40, as manifested by up-regulation of class II major histocompatibility complex and CD23 antigens. Since the xid defect has now been identified as a point mutation in the protein tyrosine kinase Btk, our results point to an important role for this kinase in the downstream signaling cascade elicited in response to ligation of either surface Ig or CD40.
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PMID:B cells from CBA/N mice do not proliferate following ligation of CD40. 751 60

We describe a probable recessive X-linked myopathy characterized by the presence of vacuolated muscle fibers. Four males and their shared maternal grandfather were affected. Clinical characteristics include juvenile onset, very slow progression, and predominant proximal muscle involvement. The clinical picture and the morphological findings are compared with those previously described in a family. By immunofluorescence, all histologically abnormal muscle fibers, in particular those vacuolated, showed a strong deposition of the complement C5b-9 membrane attack complex over the whole muscle fiber surface. Weak immunostaining for membrane attack complex was also found in endomysial capillaries and perimysial vessel walls. Muscle fibers showed sarcolemmal immunolabeling with anti-major histocompatibility complex I, which was also present on the margins of many vacuoles. All vacuoles were stained by antidystrophin antibody, which colocalized in most of them with antilaminin immunostaining. Taken together, these results suggest that the deposition of membrane attack complex on the damaged cell surface membrane could be important in the pathogenesis of this muscle disorder, and that the membrane-bounded vacuoles could be a consequence of sarcolemmal invagination.
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PMID:X-linked vacuolated myopathy: complement membrane attack complex on surface membrane of injured muscle fibers. 775 59

A unique transgenic mouse line has undergone transgene integration in a very precise fashion. The phenotype displayed by mice of the line followed the predicted inheritance patterns for X-linked transgene insertion which has been confirmed. In order to investigate the mechanism of integration the DNA sequence of the transgene and cellular junctions have been determined. A comparison between wild type and transgenic mutant sequences at the site of insertion revealed that there was no loss or rearrangement of cellular DNA upon integration of the transgene. The cellular sequences at the transgene 5' and 3' joins are contiguous in the wild type. The integrant exists as a head to tail tandem dimer with minimal loss of sequence compared with the injected monomer. Analysis of the site of insertion has revealed a 5 bp homology between the 5' end of the transgene and the cellular sequences. In addition, adjacent to the site of insertion within the cellular sequences, there are several sequence motifs implicated in recombination events including a clustering of strong consensus sites of DNA topoisomerase type I and a region of homology to the human minisatellite consensus core sequence, the Escherichia coli Chi site and the meiotic recombination hotspot within the E beta gene of the murine major histocompatibility complex. This clustering of features is likely to have been factorial in the integrity of the insertion event. A model depicting the mechanism of this precise integration is proposed.
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PMID:A model for the mechanism of precise integration of a microinjected transgene. 867 44

Bruton tyrosine kinase (Btk) is essential for the development of pre-B cells to mature B cell stages. Btk-deficient mice manifest an X-linked immunodeficiency (xid) defect characterized by a reduction of peripheral IgMlow IgDhigh B cells, a lack of peritoneal CD5+ B cells, low serum levels of IgM and IgG3, and impaired responses to T cell independent type II (TI-II) antigens. We have generated transgenic mice in which expression of the human Btk gene is driven by the murine class II major histocompatibility complex Ea gene locus control region, which provides gene expression from the pre-B cell stage onwards. When these transgenic mice were mated onto a Btk- background, correction of the xid B cell defects was observed: B cells differentiated to mature IgMlowIgDhigh stages, peritoneal CD5+ B cells were present, and serum Ig levels and in vivo responses to TI-II antigens were in the normal ranges. A comparable rescue by transgenic Btk expression was also observed in heterozygous Btk+/- female mice in those B-lineage cells that were Btk-deficient as a result of X chromosome inactivation. These findings indicate that the Btk- phenotype in the mouse can be corrected by expression of human Btk from the pre-B cell stage onwards.
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PMID:Correction of the X-linked immunodeficiency phenotype by transgenic expression of human Bruton tyrosine kinase under the control of the class II major histocompatibility complex Ea locus control region. 901 32


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