Characterization of the Chicken C-Type Lectin-Like Receptors B-NK and B-lec Suggests That the NK Complex and the MHC Share a Common Ancestral Region

Abstract

The sequencing of the chicken MHC led to the identification of two open reading frames, designated B-NK and B-lec, that were predicted to encode C-type lectin domains. C-type lectin domains are not encoded in the MHC of any animal described to date; therefore, this observation was completely unexpected, particularly given that the chicken has a “minimal essential MHC.” In this study, we describe the initial characterization of the B-NK and B-lec genes, and show that they share greatest homology with C-type lectin-like receptors encoded in the human NK complex (NKC), in particular NKR-P1 and lectin-like transcript 1 (LLT1), respectively. In common with NKR-P1 and LLT1, B-NK and B-lec are located next to each other and transcribed in opposite orientation. Like human NKR-P1, B-NK has a functional inhibitory signaling motif in the cytoplasmic tail and is expressed in NK cells. In contrast, B-lec contains an endocytosis motif in the cytoplasmic tail, and like LLT1, is an early activation Ag. Further analysis leads us to propose that there are four subgroups of C-type lectin-like receptors in the NKC, which arose as a result of duplication events. Moreover, this analysis suggests that the NKC may be considered a fifth paralogous region, and therefore shares an ancient common origin with the MHC. This provides evidence that C-type lectin-like receptors were present in the preduplication, primordial MHC region, and suggests that an original function of MHC molecules was for recognition by NK cell receptors encoded nearby.

Ancestral Organization of the MHC Revealed in the AmphibianXenopus

“…The chicken MHC contains putative NK receptors in the C-type lectin family that are most related to genes in the mammalian NK cell complex (NKC) (13,67). This finding not only demonstrates a common evolutionary origin of the NK cell complex and MHC, but also suggests coevolution of the linked NK cell and class I receptors (13,68).…”

Cutting Edge: Lectin-Like Transcript-1 Is a Ligand for the Inhibitory Human NKR-P1A Receptor

“…In mice, the LLT1 ortholog Clr-b, like MHC class I, is widely expressed (11). Recently, potential orthologs for NKR-P1A and LLT1, B-NK and B-lec, respectively, have been described in the chicken MHC region (26). This raises the questions of whether B-NK and B-lec interact, and whether NKR-P1A-LLT1-like interactions have been preserved through evolution.…”

Heterogeneous but conserved natural killer receptor gene complexes in four major orders of mammals

“…These two groups of CLSF genes, therefore, must have diverged from each other before the divergence of mammals and birds. The two previously reported chicken NKC sequences are on chromosome 16, linked to the chicken MHC (13). The genomic sequence corresponding to the first reported sequence, B-lec, has only the first two exons of the CTLD-encoding part on chromosome 16, whereas the third exon is located on an unmapped contig.…”