title: 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: BACKGROUND
  So-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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: IFR Claude de Préval, INSERM U563, CHU Purpan, 31300 Toulouse, France. laupoui@pasteur.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Lau
authors.forename: Claire
authors.initials: C
authors.lastname: Amadou
authors.forename: Hélène
authors.initials: H
authors.lastname: Brun
authors.forename: Virginie
authors.initials: V
authors.lastname: Rouillon
authors.forename: Fiona
authors.initials: F
authors.lastname: McLaren
authors.forename: Anne-France
authors.initials: AF
authors.lastname: Le Rolle
authors.forename: Margaret
authors.initials: M
authors.lastname: Graham
authors.forename: Geoffrey W
authors.initials: GW
authors.lastname: Butcher
authors.forename: Etienne
authors.initials: E
authors.lastname: Joly
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D019556:COS Cells; D002460:Cell Line; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D017124:Conserved Sequence / Q000235:genetics*; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D049452:Green Fluorescent Proteins; D006649:Histocompatibility Antigens / Q000235:genetics*; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000235:genetics*; D017072:Neostriatum / Q000166:cytology / Q000378:metabolism; D010802:Phylogeny; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D014162:Transfection
chemical_list: D018076:DNA, Complementary; D006649:Histocompatibility Antigens; D008164:Luminescent Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; C038353:histocompatibility antigens RT, rat; D049452:Green Fluorescent Proteins