Article

SEROLOGIC EVIDENCE FOR ANTIGENS CONTROLLED BY THE Ir REGION IN MICE

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Abstract

Antibodies produced in B10.D2 mice against soluble lymphocyte membrane antigens of B10.A (H-2a) mice reacted only with lymphocytes of the strains carrying the Irk region, i.e., B10.A(2R), B10.K, B10.BR, B10.HTT, AQR, A.TE, C3H, and CBA; they did not react with cells of strains carrying different Ir regions, i.e., B10.A(4R), B10, B10.M, A.SW, DBA/1. It is therefore concluded that the antigen detected with these antibodies is apparently controlled by the Ir region of the H-2 complex. The antigen is present on some T lymphocytes and absent on B lymphocytes. Its presence or absence seems to correlate with MLC and GVH reactivity.

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Chapter
The H-2 complex, the major histocompatibility complex (MHC) of the mouse, is an extremely polymorphic and pleiotrophic group of loci located in the middle section of chromosome 17 (Fig. 1) (Klein, 1975). The genetic map of the H-2 complex has traditionally been defined by the H-2K locus at the centromeric end and by the H-2D locus at the telomeric end. The serological markers for the H-2K and the H-2D regions are the classic H-2 transplantation antigens with a molecular weight of 45,000 that convey genetic restriction as targets for subpopulations of cytotoxic T cells (Zinkernagel and Doherty, 1974). The H-2D region gene codes for two independent molecular products of the D and L loci (Neuport-Sautes et al., 1978; Hansen and Sachs, 1978). The order of the H-2L and H-2D loci is not known at present and will be referred to as D(L). The H-2G region is defined by an erythrocyte-specific antigen, H-2.7 (David et al., 1975a; Klein et al., 1975). Recent studies show that this antigen is also found in the serum of H-2.7-positive strains (L. Brown, personal communication) and that it could be one of the components of the complement system (Beisel, unpublished data). The S region codes for genes controlling the quantitative levels of the C’4 complement component (Meo et al., 1975; Shreffler, 1976) as well as a sex-limited allotypic variant (Slp) of the C’ 4 molecule (Passmore and Shreffler, 1970; Roos et al., 1978).
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Article
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Article
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Article
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Chapter
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Article
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Chapter
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Chapter
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Chapter
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Article
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Chapter
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Chapter
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Article
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Article
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Article
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Article
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Article
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Article
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Article
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Chapter
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Article
Antisera directed against the I (immune response gene) segment of the murine major histocompatibility complex were prepared, and the distribution of lymphoid cells binding the antisera studied by radioautography. A clear bimodal distribution of grain counts was observed in lymph node and spleen. Bone marrow lymphocytes showed heavy but heterogeneous labelling, while thymocytes were lightly but definitely labelled. Approximately 30% of lymph node cells and 60% of spleen cells were heavily labelled. The heavily labelled cells were shown to be B cells. Ia antigens are present on plaque forming cells, but probably in smaller amounts than on resting B cells. One plasma cell tumour was studied, and was found to possess little or no Ia antigen. There was no demonstrable labelling of thoracic duct lymphocytes from preparations of T cells activated to histocompatibility antigens. However, several T cell lymphomas probably possess Ia antigens, since they were rejected when transplanted into mice differing at the I region. Overall, the data indicate that Ia antigens are expressed on at least some T cells. The Ia antigens were shown to move independently of surface immunoglobulin on B cells, demonstrating the non-identity of these molecules. Pretreatment of B cells with anti-immunoglobulin did not inhibit binding of anti-Ia sera. The Ia antigens could be capped by a sandwich technique in 75% of labelled cells. The Ia antigens were specifically precipitated from lysates of surface radioiodinated spleen cells, and the products analysed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulphate. A single specific peak of radioactivity corresponding to a molecular weight of approximately 30,000 was found. The significance of these results in relation to immune response genes, receptors for antigen on T cells, and receptors for the Fc portion of IgG on B cells, is discussed.
Article
Rabbit antiserum against B10.AQR mouse spleen and lymph node cells (RAQR), after appropriate absorption, reacted with Iak-positive spleen and lymph node cells in cytotoxic and complement-fixing indicator systems. It reacted neither with Iak-positive thymocytes nor Iak-negative thymocytes, spleen, and lymph node cells. Cryostat sections of tissue from Iak-positive and Iak-negative mice were incubated with RAQR and either rabbit anti-mouse Ig or rabbit anti-T cell globulin. With the unlabeled antibody enzyme method, RAQR-stained lymphocytes were concentrated in the B-cell regions of spleen and lymph nodes of Iak-positive CBA mice. The tissues of mice bearingI-region haplotypes different fromk were negative. Reticular cells of the T cell-supporting network were also positive in Iak mice, but liver, gall bladder, and testicular cells were not. Macrophages of both Iak-positive and -negative mice were stained by RAQR and also by heat-aggregated, peroxidase-labeled Ig. Iak-positive reticular cells survived 900 R total body irradiation and persisted after grafting with Iak-negative bone marrow. The reticular cells were also seen in a thymus which was depleted of cortisone-sensitive lymphocytes.
Article
Preliminary data have suggested that CML could be directed toward antigens of the MHC but differing from SD1 or SD2. Data presented herein, using the secondary CML test, suggest that such antigens do exist, are linked to the human MHC, are different from SD1, SD2, SD3, or MLR-S and, are probably controlled by loci outside these regions —possibly outside MLR-S. In one instance such determinants were found to be linked to a given MLR-S determinant. In this instance, there was a high linkage disequilibrium () between MLR-S and SD2 and between SD2— and SD1. The relationship of such determinants to the antigen(s) predominantly expressed on B cells, as well as their role in transplantation, deserve further study.
Article
Mixed lymphocyte reaction (MLR) stimulation by purified T and B lymphocytes and thymocytes was studied. The MLR gene products involved were localized to theH-2 complex by the use of congenic mice differing atH-2, and to loci within theH-2 complex through the use of congenic mice bearing recombinant chromosome 17. Stimulation by T cells was investigated in detail. The role of small amounts of contaminating B lymphocytes, and that of backstimulation, was found to be of minor importance. T cells and thymocytes stimulated as well as or better than B cells in combinations differing in theI, S, and possibly parts of theD end, thus suggesting that these genetic regions control cell-surface products expressed on both T and B lymphocyte populations.
Article
An antibody binding assay was used to detect the presence of Ia antigens on splenic T cells of BALB/c mice. The binding of the anti-Ia antibody was determined by reverse immune cytoadherence which detects surface Ig in a highly sensitive and reproducible manner. By this approach Ia antigens could easily be detected on 10–12% of splenic T cells isolated by nylon wool columns. The Ia + T cells became Ia- upon culture in vitro for 4 hr but 70–80% of these cells were reconstituted following short exposure to a macrophage supernate. Such supernates contain Ia antigens as shown by binding to proper antisera as well as inhibition of cytotoxicity. Removal of Ia antigens from the supernate abolished its ability to reconstitute the Ia + T cells. Removal of the Fc receptors known to be present in these supernates did not affect the ability of the supernates to reconstitute the Ia antigens on T cells. The size of the Ia antigens was estimated as less than 10,000 daltons. The Ia antigens are carried on the Fc + T cells. These data indicate that the subpopulation of Fc + T cells acquires fragments of Ia antigens released from macrophages.
Article
Immune responsiveness to IgG allotypes in the mouse was found to be controlled by an immune response gene Ir-IgG linked to the H-2 locus. This was demonstrated by the analysis of the immune response to BALB/c IgG (γ2a) myeloma proteins in mice of various H-2 types from five different linkage groups of immunoglobulin heavy chains. Antisera were examined for antibodies to idiotypic (Fab) and allotypic (Fc) specificities. No immune response to BALB/c IgG myeloma proteins was found in mice with the same heavy-chain immunoglobulin linkage group as BALB/c but of different H-2 types. In mice with immunoglobulin heavy chains that are different than BALB/c, a high immune response to IgG myeloma proteins was found in H-2 types b, bc, p, r, s, and v; a low response in a, d, k, and q. The Ir-IgG gene is controlled by a dominant autosomal gene.
Article
There are genetic differences within the major histocompatibility complex of the mouse which lead to skin graft rejection but which cannot be detected serologically. When confronted with these differences on allogeneic cells, lymphocytes proliferate in vitro. In other cases, in vitro lymphocyte proliferation but no skin graft rejection is associated with loci that are linked to but genetically separable from the loci controlling the serologically defined antigens.
Article
A new class of genes that controls the formation of specific immune responses has been identified.
Article
The immune response to BALB/c IgA myeloma proteins (Ir-IgA) was determined in mice of various H-2 types from five different linkage groups of immunoglobulin heavy chains (IgC(H)). Antisera were examined for antibodies to idiotypic (Fab) and allotypic (Fc) specificities. No immune response to IgA myeloma proteins was found in mice with the same linkage group as BALB/c but with different H-2 alleles. In mice with immunoglobulin heavy chains that are different than BALB/c, a high immune response to IgA myeloma proteins was found in H-2 types a, k, r, and s; a low response is associated with H-2(b) and H-2(d) types. Chromosome mapping of Ir-IgA genes in the H-2 locus indicate that they are on the right side of the chromosome, to the right of the Ss locus. Ir-IgA genes are controlled by dominant autosomal genes.
Serological identification of an Itregion antigen
  • V Hauptfeld
  • D Klein
  • J Klein
Hauptfeld, V., D. Klein, and J. Klein. 1973. Serological identification of an Itregion antigen. Science (Wash. D.C.). 181:167.