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

Members 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.These 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.Mature MHC class I molecules are heterotrimers composed of a heavy chain polypeptide, a light chain (β2-microglobulin) and a small molecular weight 'ligand' that is usually, but not always, peptidic in nature. In all vertebrate species studied to date, MHC class I heavy chains are encoded by several genetic loci, some of them highly polymorphic. The principal site of variation is the ligand-binding groove, formed at the apical face of the molecule by the α1-α2 co-domain of the heavy chain. Most, but not all of the MHC-encoded class I molecules characterised to date are endowed with a role in presentation of antigenic ligands to cells of the immune system that have cytolytic activity. A distinction can be ma