Ir Genes and Ia Antigens

Keyword(s):  
1977 ◽  
Vol 146 (2) ◽  
pp. 547-560 ◽  
Author(s):  
BD Schwartz ◽  
AM Kask ◽  
WE Paul ◽  
AF Geczy ◽  
EM Shevach

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.


1977 ◽  
Vol 146 (2) ◽  
pp. 561-570 ◽  
Author(s):  
E M Shevach ◽  
M L Lundquist ◽  
A F Geczy ◽  
B D Schwartz

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.


1981 ◽  
Vol 153 (5) ◽  
pp. 1113-1123 ◽  
Author(s):  
L J Rosenwasser ◽  
B T Huber

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).


1981 ◽  
Vol 153 (2) ◽  
pp. 464-469 ◽  
Author(s):  
M Michaelides ◽  
M Sandrin ◽  
G Morgan ◽  
I F McKenzie ◽  
R Ashman ◽  
...  

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.


1980 ◽  
pp. 1909-1924 ◽  
Author(s):  
H. B. Dickler ◽  
Carol Cowing ◽  
C. G. Ahmann ◽  
Karen S. Hathcock ◽  
D. H. Sachs ◽  
...  

1980 ◽  
Vol 151 (6) ◽  
pp. 1334-1348 ◽  
Author(s):  
C Bona ◽  
P K Mongini ◽  
K E Stein ◽  
W E Paul

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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