Controlling the Ir Genes

The anti-allotype antibody response to the b allotypic form of IgG2a is regulated by major histocompatibility complex (MHC)-encoded immune response (Ir) genes. Mice of d, b, p, q, r, and s haplotypes make a strong anti-allotype response on immunization with the CBPC101 myeloma protein (IgG2ab), whereas mice of the k, m, a, a1, u, and z haplotypes made no, or a very poor, response. All responder strains produce anti-IgG2ab antibodies which share common idiotypes (Id) without relation to the allelic forms of the Ig heavy-chain-constant region genes that the responding mice possess. Isoelectric focusing analysis of the anti-allotype antibodies produced in various strains of mice showed that they are of limited heterogeneity and quite similar from strain to strain. Five out of six hybridoma products with specificity for CBPC101 allotype expressed cross-reactive idiotypes (IdX). Two of hybridoma products expressing IdX identify CH3-domain determinants, and one has been assigned a CH2-domain specificity.

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Induction of a ragweed-specific allergic state in Ir-gene-restricted nonresponder mice.

Journal of Experimental Medicine ◽

10.1084/jem.146.1.302 ◽

1977 ◽

Vol 146 (1) ◽

pp. 302-307 ◽

Cited By ~ 5

Author(s):

N Chiorazzi ◽

A S Tung ◽

D H Katz

Keyword(s):

Inbred Mice ◽

Inbred Strains ◽

Antibody Responses ◽

Pollen Extract ◽

Antibody Synthesis ◽

Ige Antibody ◽

Gene Concept ◽

X Irradiation ◽

Suppressive Mechanism ◽

Ir Genes

Mice of the inbred strains, C57BL/6 and C57BL/10 (H-2b), are genetically incapable of developing IgE antibody responses to ragweed pollen extract (RE) or its dinitrophenylated derivative, DNP-RE. This nonresponsiveness has previously been thought to reflect the absence of a relevant H-2-linked Ir genes controlling responses of inbred mice to these antigens. However, pretreatment of H-2b mice with either low doses of ionizing X irradiation or cyclophosphamide abrogates the nonresponder status of such animals, apparently by removal of a suppressive mechanism normally inhibiting development of IgE responses to these antigens. The implications of these findings for mechanisms of genetic control of IgE antibody synthesis and the Ir-gene concept are discussed.

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Ir Genes, Adaptive Differentiation and Self-Recognition

Ir Genes ◽

10.1007/978-1-4612-5633-5_57 ◽

1983 ◽

pp. 409-418

Author(s):

David H. Katz

Keyword(s):

Self Recognition ◽

Ir Genes ◽

Adaptive Differentiation

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Molecular basis of fatty acid taste in Drosophila

eLife ◽

10.7554/elife.30115 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 33

Author(s):

Ji-Eun Ahn ◽

Yan Chen ◽

Hubert Amrein

Keyword(s):

Fatty Acids ◽

Behavioral Responses ◽

Hexanoic Acid ◽

Wild Type ◽

Cell Type ◽

Ionotropic Receptor ◽

Behavioral Studies ◽

Cell Type Specific ◽

Receptor Neurons ◽

Ir Genes

Behavioral studies have established that Drosophila appetitive taste responses towards fatty acids are mediated by sweet sensing Gustatory Receptor Neurons (GRNs). Here we show that sweet GRN activation requires the function of the Ionotropic Receptor genes IR25a, IR76b and IR56d. The former two IR genes are expressed in several neurons per sensillum, while IR56d expression is restricted to sweet GRNs. Importantly, loss of appetitive behavioral responses to fatty acids in IR25a and IR76b mutant flies can be completely rescued by expression of respective transgenes in sweet GRNs. Interestingly, appetitive behavioral responses of wild type flies to hexanoic acid reach a plateau at ~1%, but decrease with higher concentration, a property mediated through IR25a/IR76b independent activation of bitter GRNs. With our previous report on sour taste, our studies suggest that IR-based receptors mediate different taste qualities through cell-type specific IR subunits.

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ALLOANTISERUM-INDUCED INHIBITION OF IMMUNE RESPONSE GENE PRODUCT FUNCTION

Journal of Experimental Medicine ◽

10.1084/jem.139.3.679 ◽

1974 ◽

Vol 139 (3) ◽

pp. 679-695 ◽

Cited By ~ 45

Author(s):

Ethan M. Shevach ◽

Ira Green ◽

William E. Paul

Keyword(s):

Immune Response ◽

T Cells ◽

T Lymphocytes ◽

Cell Surface ◽

Glutamic Acid ◽

Gene Product ◽

Lymphoid Cells ◽

Immune Response Gene ◽

Ga Response ◽

Ir Genes

It has been previously demonstrated that alloantisera can specifically block the activation of T lymphocytes by antigens, the response to which is linked to the presence of histocompatibility (H) types against which the alloantisera are directed. Thus, strain 13 anti-2 serum can inhibit the activation of (2 x 13)F1 T lymphocytes by a DNP derivative of a copolymer of L-glutamic acid and L-lysine (DNP-GL), an antigen the response to which is controlled by a 2-linked Ir gene. It was proposed that alloantisera can inhibit T-lymphocyte antigen recognition through interference with the activity of immune response (Ir) gene products. In order to further study whether the inhibitory antibodies within the alloantisera are directed against H antigens or against the products of the Ir genes, we have examined whether the anti-2 serum can inhibit the function of an Ir gene (the L-glutamic acid and L-alanine [GA] gene), which is normally linked to strain 2 H genes when this gene occurs in an outbred animal lacking strain 2 H genes. In the majority of cases, the anti-2 serum was capable of inhibiting the in vitro proliferative response to GA of T cells derived from animals that were GA+2+, but the serum had little if any effect on the GA response of T cells from GA+2- animals. Furthermore, an antiserum prepared in strain 13 animals against the lymphoid cells of a GA+2- outbred animal was devoid of inhibitory activity on the GA response of cells from a (2 x 13)F1, while an antiserum prepared in strain 13 animals against the lymphoid cells of a GA+2+ outbred animal was capable of specifically inhibiting the response to GA. It thus appears that the inhibition of the GA response by the anti-2 serum is primarily mediated via antibodies directed toward strain 2 H antigens rather than antibodies specific for the product of the GA Ir gene. The mechanism of alloantiserum induced suppression of Ir gene function would then be by steric interference with the Ir gene product on the cell surface, rather than by direct binding to it. This conclusion implies that the products of both the H genes and the Ir genes are physically related on the cell surface. The implications of such a relationship in terms of the fluid-mosaic model of the lymphocyte surface are discussed.

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