Nucleotide sequence and structural analysis of the rat RT1.E u and RT1.Aw3 l genes, and of genes related to RT1.O and RT1.C

Salgar, Shashikumar K.; Kunz, Heinz W.; Gill, Thomas J.

doi:10.1007/bf00176441

Cited by 18 publications

(8 citation statements)

References 51 publications

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“…Several class I fragments have been partially sequenced. By comparison with published data, the class I exon 2 sequence of BamHI fragment 1 is nearly identical with the RT1-C c clone cc1 (23), and fragment 4 was identified as the RT1-E gene (24,25). Exon 2 sequences of fragments 2, 19, 23, and 10 revealed highest similarity (above 90%) to class Ia genes of the RT1-A region, but not to H2-D or H2-Q genes, which reside in the corresponding part of the mouse MHC.…”

Section: Class I Genesmentioning

confidence: 86%

“…It is unknown at present how many of the class I genes are indeed expressed. Among the class I genes described in the RT1-C/E/M region before, RT1-E (24,25), RT-BM1 (26,27,29), RT1-N1 (30), RT1-M3 (32), and RT1-M4 (21) have been fine mapped now, and for some of them restricted tissue distribution could be shown (Table II). Genes of the first class I cluster, such as RT1-E, as well as class I sequences obtained from this region, are more similar to rat class Ia genes than to other rat class I genes or mouse H2-D, Q, T, M genes.…”

Section: Discussionmentioning

confidence: 99%

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Physical Map and Expression Profile of Genes of the Telomeric Class I Gene Region of the Rat MHC

Ioannidu

Walter

Dressel

et al. 2001

The Journal of Immunology

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The rat is an important model for studying organ graft rejection and susceptibility to certain complex diseases. The MHC, the RT1 complex, plays a decisive role in controlling these traits. We have cloned the telomeric class I region of the RT1 complex, RT1-C/E/M, of the BN inbred rat strain in a contig of overlapping P1-derived artificial chromosome clones encompassing ∼2 Mb, and present a physical map of this MHC region. Forty-five class I exon 4-hybridizing BamHI fragments were detected, including the previously known rat class I genes RT1-E, RT-BM1, RT1-N, RT1-M2, RT1-M3, and RT1-M4. Twenty-six non-class I genes known to map to the corresponding part of the human and mouse MHC were tested and could be fine mapped in the RT1-C/E/M region at orthologous position. Four previously known microsatellite markers were fine mapped in the RT1-C/E/M region and found to occur in multiple copies. In addition, a new, single-copy polymorphic microsatellite has been defined. The expression profiles of several class I genes and the 26 non-class I genes were determined in 13 different tissues and exhibited restricted patterns in most cases. The data provide further molecular information on the MHC for analyzing disease susceptibility and underline the usefulness of the rat model.

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Section: Class I Genesmentioning

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Physical Map and Expression Profile of Genes of the Telomeric Class I Gene Region of the Rat MHC

Ioannidu

Walter

Dressel

et al. 2001

The Journal of Immunology

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“…Remarkably, the prototype gene to the class I RT1-T24 gene family was originally identified as a pseudogene in the haplotype r21 (Salgar et al 1995). In RT1 n , all four RT1-T24 genes are presumably functional, based on their coding potential.…”

Section: Genome Research 635mentioning

confidence: 99%

The Genomic Sequence and Comparative Analysis of the Rat Major Histocompatibility Complex

Hurt¹,

Walter²,

Sudbrak³

et al. 2004

Genome Res.

114

106

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We have determined the sequence of a 4-Mb interval on rat chromosome 20p12 that encompasses the rat major histocompatibility complex (MHC). This is the first report of a finished sequence for a segment of the rat genome and constitutes one of the largest contiguous sequences thus far for rodent genomes in general. The rat MHC is, next to the human MHC, the second mammalian MHC sequenced to completion. Our analysis has resulted in the identification of at least 220 genes located within the sequenced interval. Although gene content and order are well conserved in the class II and class III gene intervals as well as the framework gene regions, profound rat-specific features were encountered within the class I gene regions, in comparison to human and mouse. Class I region-associated differences were found both at the structural level, the number, and organization of class I genes and gene families, and, in a more global context, in the way that evolution worked to shape the present-day rat MHC.

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“…In the latter case, it has been clearly shown that the MAPRTLLL or MAPRTLLLL peptides resulting were unable to bind significantly to H2-Qa1 [63], and translation of those class I molecules would therefore not result in the inhibition of NK cells via their CD94/NKG2A receptors. Whilst all rat class Ia sequences where this sequence is known to start with the first methionine, this first ATG is not present in many rat class Ib molecules including RT1-C l [30] and RT1-E u [25], and the second methionine is therefore used. Since both RT1-C l and RT1-E u have been shown to be potential activators of allorecognition by NK cells [62,64], there is therefore a correlation whereby the molecules that can inhibit NK cell activity also have a functional codon for the first methionine, and the ones that can be recognised by NK activatory receptors do not.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, we have found that transcripts for molecules very closely related to those identified in placenta can also be found in neurospheres [23], which are in vitro cultures of neural stem cells [24], as well as in cDNA libraries of lymphoid tissues. Altogether, these form a group of sequences that are very closely related to one another, and more distantly to the RT1-E u molecule [25]. We have therefore chosen to name the members of this group RT1-E2, and report here on their characterisation.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of RT1-E2, a multigenic family of highly conserved rat non-classical MHC class I molecules initially identified in cells from immunoprivileged sites

et al. 2003

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BackgroundSo-called "immunoprivileged sites" are tissues or organs where slow allograft rejection correlates with low levels of expression of MHC class I molecules. Whilst classical class I molecules are recognised by cytotoxic T lymphocytes (CTL), some MHC class I molecules are called "non-classical" because they exhibit low polymorphism and are not widely expressed. These last years, several studies have shown that these can play different, more specialised roles than their classical counterparts. In the course of efforts to characterise MHC class I expression in rat cells obtained from immunoprivileged sites such as the central nervous system or the placenta, a new family of non-classical MHC class I molecules, which we have named RT1-E2, has been uncovered.ResultsMembers of the RT1-E2 family are all highly homologous to one another, and the number of RT1-E2 loci varies from one to four per MHC haplotype among the six rat strains studied so far, with some loci predicted to give rise to soluble molecules. The RT1n MHC haplotype (found in BN rats) carries a single RT1-E2 locus, which lies in the RT1-C/E region of the MHC and displays the typical exon-intron organisation and promoter features seen in other rat MHC class I genes. We present evidence that: i) RT1-E2 molecules can be detected at the surface of transfected mouse L cells and simian COS-7 cells, albeit at low levels; ii) their transport to the cell surface is dependent on a functional TAP transporter. In L cells, their transport is also hindered by protease inhibitors, brefeldin A and monensin.ConclusionsThese findings suggest that RT1-E2 molecules probably associate with ligands of peptidic nature. The high homology between the RT1-E2 molecules isolated from divergent rat MHC haplotypes is particularly striking at the level of their extra-cellular portions. Compared to other class I molecules, this suggests that RT1-E2 molecules may associate with well defined sets of ligands. Several characteristics point to a certain similarity to the mouse H2-Qa2 and human HLA-G molecules.

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Nucleotide sequence and structural analysis of the rat RT1.E u and RT1.Aw3 l genes, and of genes related to RT1.O and RT1.C

Cited by 18 publications

References 51 publications

Physical Map and Expression Profile of Genes of the Telomeric Class I Gene Region of the Rat MHC

Physical Map and Expression Profile of Genes of the Telomeric Class I Gene Region of the Rat MHC

The Genomic Sequence and Comparative Analysis of the Rat Major Histocompatibility Complex

Characterisation of RT1-E2, a multigenic family of highly conserved rat non-classical MHC class I molecules initially identified in cells from immunoprivileged sites

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