Structural organization of rat CD1 typifies evolutionarily conserved CD1D class genes

Abstract

The non-major histocompatibility complex (MHC)-encoded CD1 family has recently emerged as a new antigen-presenting system that is distinct from either MHC class I or class II molecules. In the present study, we determined the genomic structure of the rat CD1 locus. It was extremely similar to mouse CD1 genes, especially to CD1D1. The 5' flanking region of the CD1 gene contained the binding motifs for two cytokine-inducible transcription factors, NF-IL2-A and NF-IL6. Some regulatory elements found in MHC class I genes (enhancer A, enhancer B, and the IFN response element) were absent. It is of interest that a tyrosine-based motif for endosomal localization found in the human CD1b cytoplasmic tail was encoded by a single short exon which was conserved in all CD1 molecules except for CD1a. Southern blot and direct sequencing analyses of inbred rat strains suggested very limited polymorphism in the 5' region where a hydrophobic ligand-binding groove is encoded; a single base substitution resulted in amino acid alteration of alanine (GCT) to valine (GTT) at codon 119. Comparison of the overall exon-intron organization of CD1 genes revealed that the length of the intron was also characteristic to each of the two classes of CD1 genes, classic CD1 and CD1D; such categorization has hitherto been made according to the sequence similarity of the coding region. This finding provides further support for the hypothesis that the two classes have different evolutionary histories. In contrast to the complete absence of the classic CD1 in rats and mice, the entire region of nonpolymorphic CD1D has been conserved through mammalian evolution. Similar functional properties of rodent CD1 and human CD1d are implied.

The Complementarity Determining Region 2 of BV8S2 (Vβ8.2) Contributes to Antigen Recognition by Rat Invariant NKT Cell TCR

“…The rat also expresses genes for CD1d (22,23) and the AV14, AJ18 (6), and BV8S2 (24) gene segments, which are highly similar to those of the mouse (Ͼ80% sequence similarity of the translated products). Peculiar to the rat is the existence of a multimember AV14 gene family and the organ-specific preferences of certain AV14AJ18 rearrangements.…”

“…PCR product was cloned into TOPO cloning vector and sequenced. The sequence was identical with rat CD1d (GenBank accession number AB029486) published by Katabami et al (23). Mouse and rat CD1d DNA were cloned into EcoRI site of pczCGZ5IZ and pczCGZ5 IEGZ vectors, respectively, and were further used for retroviral infection of P80rCD80 cells.…”

NKT Cells in the Rat: Organ-Specific Distribution of NK T Cells Expressing Distinct Vα14 Chains

“…Two classes of CD1 genes have been identified (13,14). Whereas the classic CD1 genes were absent in rats and mice, CD1D gene has been conserved through mammalian evolution including mice, rats, rabbits, sheep, and humans (14 -19).…”

“…On the contrary, Brossay et al reported that murine CD1d was mainly expressed on hemopoietic cells but not by the epithelium of the digestive tracts (24). Therefore, from a phylogenetic standpoint, several investigators have hypothesized that CD1d molecules have a similar functional significance in various mammalian immune systems (1,13,18,25). To elucidate the immunological significance of NKT cells and their interaction with CD1d, especially in a variety of unique disease models established in rats, it is very important to obtain information about the rat invariant TCR ␣-chain.…”

The hypervariable region 4 (HV4) and position 93 of the α chain modulate CD1d‐glycolipid binding of iNKT TCRs

“…Rats have a CD1d gene whose expression pattern on hematopoietic cells is nearly identical to that of mouse CD1d, different BV8S2 homologues (BV8S2 and BV8S4), and generate typical AV14/AJ18 rearrangements [15,[18][19][20][21]. A direct identification of rat iNKT cells has been possible only recently by staining of primary rat iNKT cells with rat CD1d dimers [22].…”