Duplicated DQ haplotypes increase the complexity of restriction element usage in cattle

The RMC of cattle encodes two distinct isotypes of class II molecules, DR a nd DQ, Unlike humans, cattle lack the DP locus and about half the common ha plotypes express duplicated De genes. The number and frequency of DQA and D QB alleles means that most cattle are heterozygous. If inter- and/or intrah aplotype pairing of DQA and DQB molecules occurs, cattle carrying DQ-duplic ated haplotypes may express more restriction elements than would be predict ed by the number of expressed alleles, We are investigating whether duplica ted haplotypes cause differences in immune response, particularly in terms of generating protective immunity. We have analyzed the Ag-presenting funct ion of DQ molecules in two heterozygous animals, one of which carries a dup licated haplotype, We compared the class II isotype specificity of T cell c lones recognizing a putative vaccinal peptide from foot-and-mouth disease v irus (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 interhapl otype pairings of DQA and DQB molecules form functional restriction element s, Both animals showed distinct biases to usage of particular restriction e lements. Mainly DQ-restricted clones were derived from the animal with dupl icated DQ genes, whereas the majority of clones from the animal with a sing le DQ gene pair were DR restricted, Furthermore, haplotype bias was observe d with both animals. These experiments show that understanding of class LI chain pairing in addition to knowledge of the genotype may be important in vaccine design where effective epitope selection is essential.