Disease relevance of RT1-A

• Several genes, including those encoding keratin K7 and the u haplotype of MHC class I RT1-A, were found to be overexpressed in neu-initiated carcinomas as well as in mammary carcinomas induced by other agents, when compared to their expression in normal mammary tissue [1].
• In this report, we present data from two breeding studies utilizing the r8 haplotype (RT1AaBuDuEuCu) that demonstrate that (1) the RT1A locus is not involved in the disease association, (2) the MHC genes determining disease susceptibility are not unique to the BB rat, and (3) IDDM resistance genes are found outside the MHC [2].

High impact information on RT1-A

• This antigen system is unusual in several respects: it does not involve class I RT1A gene products usually used by killer cell responses in the rat, it maps to the major histocompatibility complex (MHC) class I-like RT1C region, and it requires homozygous expression of RT1Cav1 alleles [3].
• Immunological properties of subcellular rat lymphocyte preparations. Primary allogeneic stimulation in vitro by fractions containing Ia (RT1-B), but not RT1-A antigens [4].
• In conjunction with previous breeding studies, this study maps the diabetes susceptibility gene to the right of the RT1-A locus and to the left of the RT1-C locus [5].
• A cDNA clone encoding a RT1 E beta chain was isolated from a cDNA library prepared from Wistar (RT1 mu) spleen poly(A) RNA by screening with DNA fragments encoding a RT1 A beta chain [6].
• LEW (RT1(1)) rats were primed for indirect T cell allorecognition of DA (RT1av1) classical class I MHC molecules by immunization with synthetic 22-24 amino acid peptides corresponding to the alpha-helices of the RT1-A class I molecule [7].

Biological context of RT1-A

• Classical RT1-A class I and RT1-B class II major histocompatibility complex (MHC) molecules were purified from DA (RT1avl) spleens, and the individual chains separated and purified by preparative polyacrylamide gel electrophoresis in sodium dodecyl sulfate [8].
• Following monoclonal antibody affinity, lentil lectin affinity, and gel filtration chromatography, 600 micrograms of soluble RT1-A class I molecules with antigen activity equivalent to 1.3 x 10(11) nucleated DA spleen cells (greater than 500 DA spleens) was obtained [9].
• Alloantibodies produced as a consequence of multiple semi-allogeneic pregnancies (pregnancy-induced antisera) were directed only to RT1A antigens [10].
• Furthermore, the diabetic rats heterozygous by serotyping at the RT1A class I loci were also heterozygous at the RT1B and RT1D loci of the class II region and did not show evidence of a recombinant haplotype when examined by Southern blot analyses using molecular probes for class I and class II genes [11].

Anatomical context of RT1-A

• During mid and late pregnancy, RT1-A mainly localized in decidual blood vessels and spongiotrophoblast cells of the junction zone [12].
• In late pregnancy, expression of RT1-A decreased in placenta and increased in uterus, and RT1-DM increased in both placenta and uterus with IFN-gamma treatment compared with untreated controls [12].
• Immunohistochemical studies indicated that, in early pregnancy, RT1-DM protein mainly localized to luminal and glandular uterine epithelium, and RT1-A was present in deciduas basalis, outer layer of luminal epithelium and glandular epithelium [13].
• Interestingly, after mechanical nerve injury, glial cells predominantely upregulated expression of RT1-A, whereas neuronal expression of RT1-U remained unchanged [14].
• Individual rat cells producing antibody to rat MHC class I alloantigens ( RT1A ) and other erythrocyte (E)-associated alloantigens can be enumerated by a solid-phase antibody-forming cell focus ( AFCF ) assay [15].

Associations of RT1-A with chemical compounds

• Immunohistochemical studies suggested that in early pregnancy, RT1-DM protein mainly localized to uterine luminal epithelium and glandular epithelium, and RT1-A mainly localized to decidual blood vessels and decidua basalis [12].
• The effect of cyclosporine on the alloantibody response to blood transfusion was investigated in inbred strains of rats by IHA and CELISA; recipient animals differed from the donors at the class I (RT1A) or both class I and class II (RT1B) antigens of the major histocompatibility complex [16].
• Ursodeoxycholic acid alone or in combination with cholic acid increased the expression of RT1A compared to normal controls, of RT1B compared to AOM-treated rats, and of RT1D compared to controls or AOM-treated rats [17].

Regulatory relationships of RT1-A

• METHODS: The expression of non-classical class II major histocompatibility complex (RT1-DM) antigens and classical class I major histocompatibility complex (RT1-A) antigens induced by IFN-gamma was examined by reverse transcription-PCR, western blotting and immunohistochemistry [12].

Other interactions of RT1-A

• Effect on expression of RT1-A and RT1-DM molecules of treatment with interferon-gamma at the maternal--fetal interface of pregnant rats [12].
• Hence, it is possible to generate Ia-related allogeneic helper signals in primary, as well as secondary, in vitro responses, using subcellular membrane fragments that have restricted expression of RT1-B-, but not RT1-A-, encoded antigens [4].
• The rats were classified into 5 groups according to the differences in subregions of the RT1 (rat MHC) between the recipient and the donor: group 1, RT1-A,B,D barrier (the differences of RT1-A,B,D subregions); group 2, RT1-A barrier; group 3, RT1-B,D barrier; group 4, RT1-B barrier; and group 5, RT1-D barrier [18].
• Sequence analysis of the genomic interval between the Rps18 and RT1-A genes in the RT1u haplotype [19].

Analytical, diagnostic and therapeutic context of RT1-A

• The cellular requirements for rejection of heart grafts bearing isolated major histocompatibility complex (MHC) subregion RT1A-encoded class I disparities was assessed by adoptive transfer [20].
• Morphologic studies of acute rat cardiac allograft rejection across an isolated major histocompatibility complex class I (RT1A) disparity [21].
• Heterotopic segmental small bowel transplantation (SBT) was performed using cuff anastomoses in the inbred rat strain combination DA (RT1a) and LEW (RT1) [22].

References