High allelic polymorphism, moderate sequence diversity and diversifying selection for B-NK but not B-lec, the pair of lectin-like receptor genes in the chicken MHC

Abstract

We previously characterised the C-type lectin-like receptor genes B-NK and B-lec, located next to each other in opposite orientations in the chicken major histocompatibility complex (MHC). We showed that B-NK is an inhibitory receptor expressed on natural killer cells, whereas B-lec is an activation-induced receptor with a broader expression pattern. It is interesting to note that the chicken MHC has been linked with resistance or susceptibility to Marek's disease virus (MDV), an oncogenic herpes virus. Recent reports show that the C-type lectin-like receptors in mouse and rat (Ly49H, NKR-P1 and Clr) are associated with resistance to another herpesvirus, cytomegalovirus (CMV). Therefore, B-NK and B-lec are potential candidate genes for the MHC-mediated resistance to MDV. In this paper, we report that both genes encode glycosylated type II membrane proteins that form disulphide-linked homodimers. The gene sequences from nine lines of domestic chicken representing seven haplotypes show that B-lec is well conserved between the different haplotypes, apparently under purifying selection. In contrast, B-NK has high allelic polymorphism and moderate sequence diversity, with 21 nucleotide changes in the complementary deoxyribonucleic acids (cDNAs) resulting in 20 amino acid substitutions. The allelic variations include substitutions, an indel and loss/gain of three predicted N-linked glycosylation sites. Strikingly, there is as much as 7% divergence between protein sequences of B-NK from different haplotypes, greater than the difference observed between the highly polymorphic human KIR NK receptors. Analysis of ds and dn reveal evidence of strong positive selection for B-NK to be polymorphic at the protein level, and modelling demonstrates significant variation between haplotypes in the predicted ligand binding face of B-NK.

Defining the Turkey MHC: Sequence and Genes of the B Locus

“…Indeed, even within chicken haplotypes, it is under the highest level of selection (40). This level of selection suggests this gene may have a significant role in immunology and supports the suggestion that an allele of this locus in chickens may be responsible for the genetic resistance to Marek's disease long associated with the B21 haplotype (12,17,43,53).…”

Specific alleles at immune genes, rather than genome‐wide heterozygosity, are related to immunity and survival in the critically endangered Attwater's prairie‐chicken

“…The function of Blec1 is not well known in birds, but it has high amino acid similarity to CD69, an early activation antigen within the natural killer gene family (Shiina et al . ; Rogers & Kaufman ). In humans, CD69 may be important in regulating an inflammatory immune response, and some allelic variants are associated with chronic inflammatory diseases (González‐Amaro et al .…”

The peptide motif of the single dominantly expressed class I molecule of the chicken MHC can explain the response to a molecular defined vaccine of infectious bursal disease virus (IBDV)

“…Many investigators, including ourselves, have characterised genes located on the chicken MHC microchromosome that in other animals are found in regions of the MHC, adjacent to the MHC, or in MHC paralogous regions (Afanassieff et al 2001; Briles et al 1993; Guillemot et al 1988; Kaufman et al 1999a; Maruoka et al 2005; Miller et al 1994a, b, 1996, 2005; Rogers et al 2005; Rogers and Kaufman 2008; Ruby et al 2005; Salomonsen et al 2003, 2005; Shiina et al 2007). This has led to an alternative view that the chicken MHC is in fact very large and complex, containing many genes located in at least two separate regions, called MHC-B and MHC-Y (Afanassieff et al 2001; Delany et al 2009; Miller et al 1996; Solinhac et al 2010).…”