Specificity of Immune Response Control by H-Linked Ir Genes

1976 ◽  
pp. 189-201
Author(s):  
E. Rüde ◽  
E. Günther
Keyword(s):  
Immune Response ◽  
Response Control ◽  
Ir Genes

scholarly journals ALLOANTISERUM-INDUCED INHIBITION OF IMMUNE RESPONSE GENE PRODUCT FUNCTION

1974 ◽  
Vol 139 (3) ◽  
pp. 679-695 ◽  
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.

scholarly journals The guinea pig I region. I. A structural and genetic analysis

1977 ◽  
Vol 146 (2) ◽  
pp. 547-560 ◽  
Author(s):  
BD Schwartz ◽  
AM Kask ◽  
WE Paul ◽  
AF Geczy ◽  
EM Shevach
Keyword(s):  
Immune Response ◽  
Genetic Analysis ◽  
Guinea Pig ◽  
Disulfide Bonds ◽  
Chemical Structure ◽  
Characteristic Structure ◽  
Ia Antigens ◽  
Region I ◽  
Ir Genes

The Ia antigens of the guinea pig have been shown to play a central role in the regulation of the immune response. We have previously partially characterized the chemical structure of these antigens. In this communication, we further characterize the structure of the five Ia antigens already described, as well as two new Ia antigens. Evidence is presented which shows that these seven Ia antigens can be organized into three distinct groups, each with a characteristic structure. The Ia.2 determinant of strain 2 and the Ia.3 and Ia.5 determinants of strain 13 animals are found on molecules composed of a 25,000 dalton chain and a 33,000 dalton chain in noncovalent association, or else are individually expressed on nonlinked 33,000 and 25,000 dalton molecules. The Ia.4 and Ia.5 determinants of strain 2 and the Ia.7 determinant of strain 13 are borne on 58,000 dalton molecules in which two chains are linked by disulfide bonds. The Ia.1 and Ia.6 determinants of strain 13 are found on a molecule of 26,000-27,000 daltons. Ia.6 of strain 2 has yet to be definitively assigned. Furthermore, in strain 13 animals the Ia.3 and Ia.5 determinants are borne on the same molecule, as are the Ia.1 and Ia.6 determinants. In strain 2 animals, the Ia.4 and Ia.5 determinants are found on the same molecule. On the basis of chemical structure, we have divided the guinea pig I region into three subregions. The accompanying paper presents evidence of associations between particular Ia genes and Ir genes.

scholarly journals Multiple H-2-linked immune response gene control of H-2D- associated T-cell-mediated lympholysis to trinitrophenyl-modified autologous cells: Ir-like genes mapping to the left of I-A and within the I region

1976 ◽  
Vol 144 (6) ◽  
pp. 1701-1706 ◽  
Author(s):  
A Schmitt-Verhulst ◽  
GM Shearer
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Immune Response Gene ◽  
Transplantation Antigen ◽  
Additional Contribution ◽  
Effector Cells ◽  
Congenic Strains ◽  
Chemically Modified ◽  
Cytotoxic Responses ◽  
Ir Genes

One of the more recent associations of the murine H-2 major histocompatibility complex (MHC) with immune function has been the finding that cytotoxic T-effector cells generated by sensitization with viral-infected (1-6), chemically modified (7-9), or weak transplantation antigen-associated (10,11) syngeneic cells can efficiently lyse target cells which express the same viral, chemical, or weak antigenic agent, and which share the H-2K and/or H-2D regions of the MHC with the responding and/or stimulating cells. Furthermore, an additional contribution of a gene(s) within the H-2 complex has been demonstrated which controls immune response potential (Ir genes) in the generation of cytotoxic effector cells to trinitrophenyl (TNP)-modified self components (12,13). In such studies it was found that certain B10 congenic strains generated good cytotoxic responses to both TNP- modified H-2K and H-2D region products, whereas other B10 congenic strains exhibited preferential or exclusive reactivity against TNP-modified H-2K region products. Some of these recombinant strains differing in response potential to TNP- modified H-2D products expressed the same haplotype at the D end, but differed at the K end of H-2. The low responsiveness observed in the B10.A strain to TNP-modified H-2D(d) when compared to B10.D2 and (B10.A x B10.D2)F(1) for the same specificity, suggested a role of dominant Ir genes which map in K, I-A, I-B, I-J, and/or I-E (12, 14). In the present report an attemnpt was made to further map within the MHC the Ir gene(s) controlling cell-mediated lympholysis (CML) to TNP-modified H-2D(d), by using recombinant mouse strains on the A and B10 backgrounds. Irrespective of the genetic background, the s and k haplotypes at the K end generated high and low cytotoxic responses, respectively, to H-2D(d)-TNP. The intermediate responder and low responder status of the A.TL and A.AL strains, respectively, indicated that a gene mapping in the K region of H-2 influences response potential. Furthermore, the differences in the levels of cytotoxicity detected in the A.TH and A.TL strains suggested an additional I region influence. Taken together these findings raise the possibility that multiple genes mapping within different regions of the MHC control the level of T-cell-mediated cytotoxicity to chemically modified autologous cells.

scholarly journals Genetic control of the immune response to staphylococcal nuclease. IV. H-2-linked control of the relative proportions of antibodies produced to different determinants of native nuclease.

1977 ◽  
Vol 145 (1) ◽  
pp. 123-135 ◽  
Author(s):  
J A Berzofsky ◽  
A N Schechter ◽  
G M Shearer ◽  
D H Sachs
Keyword(s):  
Immune Response ◽  
B Cells ◽  
Antibody Response ◽  
Binding Capacity ◽  
Staphylococcal Nuclease ◽  
Gene Control ◽  
Low Responder ◽  
Selection Of ◽  
Ir Genes

The relative proportions of antibodies of different specificities within antisera raised to native staphylococcal nuclease have been studied in several strains of mice in which the antibody response has been shown to be under H-2-linked Ir-gene control. A method was developed in which binding to different radiolabeled fragments of nuclease was titrated against increasing fragment concentration until the binding capacity of the antiserum for that fragment was saturated. In comparing the low responder (H-2b) strain C57BL/10 with its congenic high responder counterpart B10.A (H-2a), it was found that the two strains made markedly and reproducibly different proportions of antibodies to different determinants on native nuclease. Since these two strains differ only at H-2, and therefore have identical immunoglobulin structural gene repertoires, we conclude that H-2-linked Ir genes can control the response to different determinants on the same antigen molecule independently of one another. This result suggests a possible role of H-2-linked genes in the selection of specific B cells.

scholarly journals HLA and immune response control.

1995 ◽  
Vol 18 (6) ◽  
pp. 595-596
Author(s):  
TAKEHIKO SASATSUKI
Keyword(s):  
Immune Response ◽  
Response Control

scholarly journals The xid gene controls Ia.W39-associated immune response gene function.

1981 ◽  
Vol 153 (5) ◽  
pp. 1113-1123 ◽  
Author(s):  
L J Rosenwasser ◽  
B T Huber
Keyword(s):  
Immune Response ◽  
Gene Function ◽  
Immune Response Gene ◽  
T Cell Proliferation ◽  
Response Gene ◽  
Histocompatibility Complex ◽  
Ia Antigens ◽  
Antigen Presenting ◽  
Ir Genes

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).

Sign in / Sign up

Export Citation Format

Share Document