The complete sequence of the MHC class II chain RT1Dα^uof the diabetic BB rat: mRNA levels of RT1.Dα in lymphocytes

Abstract

The major histocompatibility complex of the rat (RT1 complex) encodes two sets of class II molecules referred to as RT1.B and RT1.D. The complete structure of the RT1.D alpha u chain of the diabetes prone BB rat was determined by the isolation and characterization of a full size cDNA. Comparisons of the nucleotide and protein sequences of RT1.D alpha with the analogous molecules, H-2 I-E alpha and HLA DR alpha, revealed that these alpha chains have been highly conserved during evolution. Southern blot analysis indicated an association of the RT1 haplotypes, 'u' and 'l', with Bam H1 DNA bands of 9.8 kb and 11.7 kb, respectively. The BB rat develops insulin dependent diabetes as an autoimmune abnormality. Accumulating evidence suggests a cellular mediated etiology and the involvement of class II molecules. The steady state levels of RT1.D alpha mRNA were measured in splenic lymphocytes of diabetes prone BB rats and age matched histocompatible normal nondiabetic WF rats by a RNase protection assay. Compared to WF rats, elevated transcripts of RT1.D alpha were found in lymphocytes of young BB rats (approximately 4x and approximately 2.5x greater at 20-40 and 40-75 d, respectively). In lymphocytes of older diabetic and nondiabetic BB rats (greater than 75 d) the levels of RT1.D alpha mRNA were lower than in the young BB rats and were found at the WF control levels. The increased steady state RT1.D alpha mRNA levels in the young BB rats may reflect differences in the proportion of splenic lymphocytes expressing this gene (activated lymphocytes), and thus differences in splenic lymphocyte populations. The steady state RT1.D alpha mRNA levels in lymphocytes of the normal rats were found to be relatively similar at all ages examined. The increased class II gene transcripts found in lymphocytes of young BB rats indicates that they possess a highly activated immune system.

Mitomycinoid Alkaloids: Mechanism of Action, Biosynthesis, Total Syntheses, and Synthetic Approaches

“…At the carbamate carbon (C10) 2,7-DAM ( 36 , Scheme ) monoalkylates DNA in the major groove at guanine N7 of (G) n tracts. , The selectivity correlates with the sequence specificity of the negative molecular electrostatic potential of the major groove, suggesting that the alkylation selectivity of 2,7-DAM is determined by sequence-specific variation of the reactivity of the DNA . This may not be surprising considering that N7 is the most nucleophilic position of guanine , and that the less reactive carbamate alkylating function has been shown to follow patterns of reactivity characteristic of S N 2 displacement. − This adduct is nontoxic, and since reduction of MC in vivo or in vitro converts most of the drug to the nontoxic quinone 2,7-DAM, this process may be regarded as an additional detoxification mechanism. , …”

Presentation of donor major histocompatibility complex class II antigens by dna vaccination prolongs heart allograft survival

“…The coding region for RT1D␣ u consisted of an 881-bp Pst I fragment from the plasmid RT1.D␣ u -11. This was subcloned into the Pst I site in pcDNA3.1Zeo to generate the plasmid pZRT1.D␣ u (16). This plasmid was digested with Nru I/Pvu II, and the 1,839-bp fragment consisting of the human cytomegalovirus promoter RT1.D␣ u cDNA and SV40 polyA signal was subcloned into the Nru I site of pZRT1.D␤ u to generate the final pZRT1.D␣/␤ u plasmid.…”

Bioinformatics analysis of the wheel treadmill test on motor function recovery after spinal cord injury

“…Fcer1g , a high‐affinity IgE receptor, is a key molecule involved in allergic reactions 36 . The proteins encoded by RT1‐DA and Ccl4 were also associated with inflammatory function 37,38 . Also, immune response and inflammatory response are the key pathological processes after SCI 28 .…”

“… 36 The proteins encoded by RT1‐DA and Ccl4 were also associated with inflammatory function. 37 , 38 Also, immune response and inflammatory response are the key pathological processes after SCI. 28 Jogia retrospectively analyzed 161 patients with SCI and found that early control of SCI‐induced systemic immune response was beneficial to longer‐term recovery.…”