Duplicated DQ haplotypes increase the complexity of restriction element usage in cattle
Duplicated DQ haplotypes increase the complexity of restriction element usage in cattle
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DOI：
10.4049/jimmunol.165.1.134
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发表时间：
2000-07-01
影响因子：
4.4
通讯作者：
Russell, GC
中科院分区：
文献类型：
--
作者：
Glass, EJ;Oliver, RA;Russell, GC
牛的RMC编码两种不同的II类分子同型，DR和DQ。与人类不同，牛缺乏DP位点，大约一半的常见单倍型表达重复的De基因。DQA和DQB等位基因的数量和频率意味着大多数牛是杂合的。如果DQA和DQB分子发生单倍型间和/或单倍型内配对，携带dq重复单倍型的牛可能表达比表达等位基因数量预测的更多的限制性元件。我们正在研究重复单倍型是否会导致免疫反应的差异，特别是在产生保护性免疫方面。我们在两只杂合动物中分析了DQ分子的ag呈递功能，其中一只携带一个重复的单倍型，我们比较了识别口蹄疫病毒（FMDV15）疫苗肽的T细胞克隆的II类同型特异性。我们首次证明牛T细胞可以识别DQ分子背景下的Ag。我们还提供证据表明，DQA和DQB分子的单倍型间配对形成了功能限制元件，两种动物都对特定限制元件的使用表现出明显的偏好。DQ限制性克隆主要来源于DQ基因重复的动物，而DQ基因对单一的动物克隆主要来源于DR限制性克隆，且两种动物均存在单倍型偏倚。这些实验表明，除了了解基因型外，了解LI类链配对在疫苗设计中可能很重要，因为有效的表位选择是必不可少的。
The RMC 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 De 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 LI chain pairing in addition to knowledge of the genotype may be important in vaccine design where effective epitope selection is essential.