Genomic location and characterisation of nonclassical MHC class I genes in cattle

Abstract

The cattle major histocompatibility complex (MHC) region contains a variable number of classical class I genes encoding polymorphic, ubiquitously expressed molecules with a role in antigen presentation. Class I cDNA sequences have previously been reported that are thought to derive from putative nonclassical class I genes. We have located four nonclassical class I genes within the cattle genome; three are close to the MIC genes, and one is close to the classical class I genes. The genomic position relative to anchor genes is very similar to the arrangement reported in the pig MHC region. We have designed gene-specific oligonucleotide primers with which to investigate the presence of these genes in distinct and well-defined MHC haplotypes and to assess transcription in different cell types. Analysis and comparison of all sequences allows an assessment of allelic variation in each case. Partial characterisation gives an indication of the possible role and likely importance of each of these genes.

Constraints on haplotype structure and variable gene frequencies suggest a functional hierarchy within cattle MHC class I

“…NC1 appears to be present on most cattle class I haplotypes, certainly on the most commonly seen configurations 1, 4, 8 and 10 (Birch et al 2008), and as described above, gene 2 is also usually present. Since the two class I regions shown in Fig.…”

“…3b, which includes intron sequences over the same region, also supports this hypothesis with NC1in this case clustering strongly within the classical gene clade. Our previous studies, using MHC homozygous animals, showed that NC1 is present on a range of distinct haplotype structures (Birch et al 2008), whereas presence of the other nonclassical genes, NC2-NC4, is more variable. A study of immune evasion by bovine papillomavirus-4 demonstrated that while expression of classical MHC class I genes was greatly reduced, NC1 continued to be strongly expressed at the surface of infected cells (Araibi et al 2006).…”

“…Figure 1 clearly demonstrates that all classical alleles cluster into the six previously defined gene groups and these gene definitions have been used for all subsequent analyses. Incorporation of the non-classical genes into this analysis indicates it is likely that the classical genes shared a common ancestor most recently with the non-classical class I gene NC1, and not with NC2, NC3 or NC4 (Birch et al 2008). This classical/non-classical relationship is well supported and remains intact irrespective of methodology.…”

Cattle MHC nomenclature: is it possible to assign sequences to discrete class I genes?

“…There are two sequences suffixed 'N' for 'null', N*03201N and N*03301N. In addition, there are 17 non-classical (NC) MHC class I sequences already assigned to mapped genes (NC1-NC4, Birch et al 2008). NC1 currently has eight alleles plus a number of splice variants, NC2 has three alleles, NC3 has a single allele and NC4 has four alleles.…”

Transcription of non-classic major histocompatibility complex (MHC) class I in the bovine placenta throughout gestation and after Brucella abortus infection

“…Although the function of bovine NC1 is largely unknown, it is thought that NC1, with its large number of splicing variants (Birch et al, 2008b), generates proteins that are anchored in the membrane or soluble, which may modulate immune tolerance in cattle (Davies et al, 2006).…”