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

Abstract

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.

Transcription variants of SLA-7, a swine non classical MHC class I gene

“…In mouse, the H2-QaI gene is orthologous to HLA-E [ 5 ] and functional homologies have been established between H2-Qa2 and HLA-G [ 6 ]. One to four MHC class Ib genes have been identified in rat according to haplotypes [ 7 ] and four MHC class Ib genes have been characterized in cattle [ 8 ]. There is a growing interest in addressing the role of the MHC class Ib genes in the species where they are characterized.…”

Extracellular matrix-associated gene expression in adult sensory neuron populations cultured on a laminin substrate

“…The MT-MMP1 nuclear staining in particular was punctate and quite distinct (Figure 9I, arrowheads), but the role of MT-MMP1 in the nucleus is not clear. RT1 (which was relatively highly expressed in both populations at t=24LN) detects a non-classical MHC-class 1 antigen specific to rat cells [29] and the staining shows enrichment on the surface of the neurons (Figure 9K, arrows). Supplemental Figure 3 and 4 present IHC for these same proteins, but showing double staining for pairs of antibodies along with IB4-labelling of the sections.…”

“…RT1-Aw2 is an MHC class I molecule [29], and MHC class I molecules have recently been implicated in the immunoregulatory functions of synaptic plasticity after nerve injury [68] and in neuroinflammation [69]. This could suggest that RT1-Aw2 plays a key role in antigen presentation and neuro-immune interactions in these cultured adult neurons.…”