Duplicated DQ Haplotypes Increase the Complexity of Restriction Element Usage in Cattle

Abstract

The MHC of cattle encodes two distinct isotypes of class II molecules, DR and DQ. Unlike humans, cattle lack the DP locus and about half the common haplotypes express duplicated DQ genes. The number and frequency of DQA and DQB alleles means that most cattle are heterozygous. If inter- and/or intrahaplotype pairing of DQA and DQB molecules occurs, cattle carrying DQ-duplicated haplotypes may express more restriction elements than would be predicted by the number of expressed alleles. We are investigating whether duplicated haplotypes cause differences in immune response, particularly in terms of generating protective immunity. We have analyzed the Ag-presenting function of DQ molecules in two heterozygous animals, one of which carries a duplicated haplotype. We compared the class II isotype specificity of T cell clones recognizing a putative vaccinal peptide from foot-and-mouth disease virus (FMDV15). We show for the first time that bovine T cells can recognize Ag in the context of DQ molecules. We also present evidence that interhaplotype pairings of DQA and DQB molecules form functional restriction elements. Both animals showed distinct biases to usage of particular restriction elements. Mainly DQ-restricted clones were derived from the animal with duplicated DQ genes, whereas the majority of clones from the animal with a single DQ gene pair were DR restricted. Furthermore, haplotype bias was observed with both animals. These experiments show that understanding of class II chain pairing in addition to knowledge of the genotype may be important in vaccine design where effective epitope selection is essential.

Identification of Major Histocompatibility Complex Restriction and Anchor Residues of Foot-and-Mouth Disease Virus-Derived Bovine T-Cell Epitopes

“…6). This is supported by recent publications showing that DQ molecules in cattle are relevant for peptide presentation to T helper cells in immune responses against FMDV-derived peptides (15), Babesia bovis (26), and Anaplasma marginale (6). Furthermore, FIG.…”

Major Histocompatibility Complex Class II DR-Restricted Memory CD4+T Lymphocytes Recognize Conserved Immunodominant Epitopes ofAnaplasma marginaleMajor Surface Protein 1a

“…Although not directly tested, this result could be explained by intrahaplotype pairing of DQ␣ and DQ␤ chains, which has been previously observed for cattle (32).…”

“…Each haplotype expresses one nonpolymorphic DR␣ molecule, one polymorphic DR␤ molecule (DRB3), and one or more polymorphic DQ␣ and DQ␤ molecules when DQ is duplicated (reviewed in reference 33). Furthermore, in cattle DQ␣ and DQ␤ chains can form both inter-and intrahaplotype pairing (32,33), resulting in increased class II polymorphism. To determine whether responses of individual Thcell clones were restricted by DR or DQ molecules, T cells were cultured with specific antigen and autologous APC, APC fully matched for both DR-DQ haplotypes, APC matched for one DR-DQ haplotype, or APC mismatched for both haplotypes (Table 2).…”

Genetic variations in the UTR of genes related to molting in Eriocheir sinensis

“…The fact that all individuals had more than two haplotypes suggested that these haplotypes did not arise from the same locus and, thus, could be regarded as evidence for the existence of gene duplication at the UTR of the ERP gene in E. sinensis. Gene duplications have been revealed in D-loop of mtDNA (Cjetva et al, 1992;Ludwig et al, 2000) and in many MHC loci, for example, the spotted seal (Phoca largha) DRB locus (Gao et al, 2015) and the cattle (Bos taurus) DQA and the DQB loci (Glass et al, 2000).…”