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 The guinea pig I region. II. Functional analysis.

1977 ◽  
Vol 146 (2) ◽  
pp. 561-570 ◽  
Author(s):  
E M Shevach ◽  
M L Lundquist ◽  
A F Geczy ◽  
B D Schwartz
Keyword(s):  
Functional Analysis ◽  
Cell Proliferation ◽  
T Cell ◽  
Immune Responses ◽  
Guinea Pig ◽  
T Cell Proliferation ◽  
Ia Antigen ◽  
Ia Antigens ◽  
Region Ii ◽  
Ir Genes

We have examined whether an association exists between specific Ia antigen genes and Ir genes which are encoded within the same haplotype. Functionally monospecific sera to the Ia antigens of the guinea pig MHC were selective in their ability to inhibit antigen-specific T-cell proliferation and we were thus able to demonstrate an association between individual Ia specificities and specific Ir genes. The results of these studies in inbred animals were confirmed by examining the association of Ir genes and Ia antigens in the outbred guinea pig population. Of great interest was the observation that antisera made against cross-reactive Ia antigens of strains lacking specific Ir genes would still inhibit immune responses of strains possessing the Ir gene, if the Ir gene was associated with that Ia antigen in the responder strain.

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).

scholarly journals Ir gene function in an I-A subregion mutant B6.C-H-2bm12.

1981 ◽  
Vol 153 (2) ◽  
pp. 464-469 ◽  
Author(s):  
M Michaelides ◽  
M Sandrin ◽  
G Morgan ◽  
I F McKenzie ◽  
R Ashman ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Cytotoxic T Lymphocytes ◽  
Gene Control ◽  
Lymphocyte Response ◽  
Ia Antigens ◽  
Male Specific ◽  
Relationship Of ◽  
The Relationship ◽  
Ir Genes

The B6.C-H2bm12 (bm 12) strain has a mutation in the I-A subregion of the murine H-2 complex and is characterized by a loss of serologically detected Ia antigens and a strong graft rejection and mixed lymphocyte response between parent and mutant. It was presumed that the mutation affected the Ia-1 gene and to determine the relationship of Ia antigens and Ir genes, the immune responses of mutant and parent were compared. The immune responses to poly(L-Tyr,LGlu)-poly(DLAla)--poly(LLys), poly(Phe,Glu)-poly(DLAla)--poly(LLys), and poly(His,Glu)-poly(DLAla)--poly(LLys) in parent and mutant were same, indicating the Ia-1 and the Ir genes for these antigens are not identical. By contrast, although C57BL/6 gave a good response, the mutant strain was unable to generate cytotoxic T lymphocytes to the male-specific H-Y antigen--a response under I-A subregion Ir gene control, which now must be considered to be the Ia-1 gene. In addition, complementary Ir genes in the H-2b haplotype for the H-Y immune response could be detected when the bm12 mutant was used.

scholarly journals Structural characteristics of the alloantigens determined by the major histocompatibility complex of the guinea pig.

1976 ◽  
Vol 143 (3) ◽  
pp. 541-558 ◽  
Author(s):  
B D Schwartz ◽  
A M Kask ◽  
W E Paul ◽  
E M Shevach
Keyword(s):  
Major Histocompatibility Complex ◽  
Guinea Pig ◽  
Disulfide Bonds ◽  
Structural Characteristics ◽  
Sodium Dodecyl ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Ia Antigens ◽  
Lentil Lectin ◽  
Nonionic Detergent

The GPLA B and Ia (I region-associated) antigens are the products of genes found in the guinea pig major histocompatibility complex. Because of their importance in immune response phenomena, a structural study of these antigens was undertaken. [3H]leucine and [3H]fucose were internally incorporated into guinea pig lymph node cells. The GPLA B and Ia antigens were solubilized by the nonionic detergent Nonidet P-40, purified by affinity chromatography using an adsorbent column of lentil lectin, isolated by immunoprecipitation, and examined by discontinuous polyacrylamide-sodium dodecyl sulfate gel electrophoresis. The GPLA antigens B.1, B.2, B.3, and B.4, were shown to be glycoproteins of mol wt 40,000 daltons and to be noncovalently associated with a 12,000 dalton protein. The molecules bearing B.2 and B.3 in a B.2/B.3 heterozygote are shown to be separable, suggesting the antigenic determinant is a primary gene product. In addition, a new GPLA determinant, S, which resembles the B antigen in that it is found on a molecule of approximately 40,000 daltons, was studied. In a B.2/B.3 S+ animal the molecule bearing antigen S was shown to be independent of those bearing B.2 and B.3, providing evidence that the genes determining B and S are at separate loci. The Ia-bearing molecules identified by anti-Ia.2,4 are glycoproteins of mol wt 58,000 daltons which are composed of two subunits of 33,000 and 25,000 daltons, respectively, linked by disulfide bonds. The Ia-bearing molecules are independent of GPLA-bearing molecules, indicating different loci determining these antigens. By all criteria, the guinea pig GPLA B antigens appear homologous to the murine H-2D and H-2K antigens, while the guinea pig Ia antigens appear homologous to the Ia antigens of the mouse.

scholarly journals Adaptive Evolution of Relish, a Drosophila NF-κB/IκB Protein

Genetics ◽  
2000 ◽  
Vol 154 (3) ◽  
pp. 1231-1238 ◽  
Author(s):  
David J Begun ◽  
Penn Whitley
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Genetic Analysis ◽  
Adaptive Evolution ◽  
Strong Evidence ◽  
Population Genetic ◽  
Microbial Pathogens ◽  
Population Genetic Analysis ◽  
Evolutionary Conflict ◽  
A Site

Abstract NF-κB and IκB proteins have central roles in regulation of inflammation and innate immunity in mammals. Homologues of these proteins also play an important role in regulation of the Drosophila immune response. Here we present a molecular population genetic analysis of Relish, a Drosophila NF-κB/IκB protein, in Drosophila simulans and D. melanogaster. We find strong evidence for adaptive protein evolution in D. simulans, but not in D. melanogaster. The adaptive evolution appears to be restricted to the IκB domain. A possible explanation for these results is that Relish is a site of evolutionary conflict between flies and their microbial pathogens.

S-Ethylthiotrifluoroacetate Enhancement of the Immune Response to Halothane in the Guinea Pig

1991 ◽  
pp. 739-744 ◽  
Author(s):  
Kenneth L. Hastings ◽  
Susan Schuman ◽  
Alan P. Brown ◽  
Cindy Thomas ◽  
A. Jay Gandolfi
Keyword(s):  
Immune Response ◽  
Guinea Pig

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.

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