Abstract
The leukocyte receptor complex (LRC) in humans encodes many receptors with immunoglobulin-like (Ig-like) extracellular domains, including the killer Ig-like receptors (KIRs) expressed on natural killer (NK) cells among others, the leukocyte Ig-like receptors (LILRs) expressed on myeloid and B cells, and an Fc receptor (FcR), all of which have important roles in the immune response. These highly-related genes encode activating receptors with positively-charged residues in the transmembrane region, inhibitory receptors with immuno-tyrosine based motifs (ITIMs) in the cytoplasmic tail, and bi-functional receptors with both. The related chicken Ig-like receptors (ChIRs) are almost all found together on a microchromosome, with over 100 activating (A), inhibitory (B), and bi-functional (AB) genes, bearing either one or two extracellular Ig-like domains, interspersed over 500–1,000 kB in the genome of an individual chicken. Sequencing studies have suggested rapid divergence and little overlap between ChIR haplotypes, so we wished to begin to understand their genetics. We chose to use a hybridization technique, reference strand-mediated conformational analysis (RSCA), to examine the ChIR-AB1 family, with a moderate number of genes dispersed across the microchromosome. Using fluorescently-labeled references (FLR), we found that RSCA and sequencing of ChIR-AB1 extracellular exon gave two groups of peaks with mobility correlated with sequence relationship to the FLR. We used this system to examine widely-used and well-characterized experimental chicken lines, finding only one or a few simple ChIR haplotypes for each line, with similar numbers of peaks overall. We found much more complicated patterns from a broiler line from a commercial breeder and a flock of red junglefowl, but trios of parents and offspring from another commercial chicken line show that the complicated patterns are due to heterozygosity, indicating a relatively stable number of peaks within haplotypes of these birds. Some ChIR-AB1 peaks were found in all individuals from the commercial lines, and some of these were shared with red junglefowl and the experimental lines derived originally from egg-laying chickens. Overall, this analysis suggests that there are some simple features underlying the apparent complexity of the ChIR locus.
Highlights
Many genes that encode type 1 transmembrane (TM) proteins with one to three extracellular C2-type immunoglobulin-like (Iglike) domains are located together on human chromosome 19, in a region that has come to be known as the leukocyte receptor complex (LRC)
killer cell Ig-like receptors (KIRs) molecules are expressed on natural killer (NK) cells as well as invariant NK T cells, with the inhibitory KIRs binding classical class I molecules of the major histocompatibility complex (MHC) as ligands, while the activating KIRs bind a variety of ligands typically related to class I molecules, encoded by either host or pathogens
A large number of cDNA and genomic DNA (gDNA) sequences from the chicken lines M11 and R11 [15] were compared to find suitably conserved short sequences from which to design oligonucleotide primers that would bind to every chicken Ig-like receptors (ChIRs)-AB1 gene, with the ones chosen amplifying a fragment of 230 nucleotides, with the central 190 nucleotides corresponding to the gene sequence between the primers
Summary
Many genes that encode type 1 transmembrane (TM) proteins with one to three extracellular C2-type immunoglobulin-like (Iglike) domains are located together on human chromosome 19, in a region that has come to be known as the leukocyte receptor complex (LRC) These genes in humans include the killer cell Ig-like receptors (KIRs), the leukocyte Ig-like receptors (LILRs), and a receptor that binds to the C-terminal region of certain antibodies (FcR), among others. These receptors either confer inhibition by having a long cytoplasmic tail with an immuno-tyrosine inhibitory motif (ITIM), or confer activation by having a positively-charged amino acid in the TM region that allows interaction with other TM proteins with cytoplasmic tails bearing immuno-tyrosine activating motifs (ITAMs). The MHC class I genes that are recognized by KIRs are highly polymorphic, and the level of interaction between these receptors and their ligands (at the genetic level called epistasis) has enormous effects on the immune response to infectious pathogens and cancer, on autoimmunity and on reproduction [reviewed in [2, 3]]
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