Identification of Major Histocompatibility Complex Restriction and Anchor Residues of Foot-and-Mouth Disease Virus-Derived Bovine T-Cell Epitopes
Identification of Major Histocompatibility Complex Restriction and Anchor Residues of Foot-and-Mouth Disease Virus-Derived Bovine T-Cell Epitopes
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DOI：
10.1128/jvi.01534-08
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发表时间：
2009-05-01
影响因子：
5.4
通讯作者：
Saalmueller, Armin
中科院分区：
文献类型：
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作者：
Gerner, Wilhelm;Hammer, Sabine E.;Saalmueller, Armin
尽管过去20年来对口蹄疫病毒（FMDV）感染后牛T细胞表位的鉴定进行了深入研究，但对主要组织相容性复合体（MHC）限制和此类表位的锚残基的了解仍然很少。因此，作为第一步，我们测试了淋巴细胞从两个实验FMDV血清型A24免疫和攻击牛识别FMDV衍生的十五肽在增殖试验。鉴定了两个表位：结构蛋白1D内的氨基酸残基66至80和结构蛋白1A内的氨基酸残基22至36。后一个表位被来自两头牛的淋巴细胞识别。通过羧基荧光素二乙酸琥珀酰亚胺酯增殖试验鉴定，CD4（+）T辅助细胞的应答引起肽特异性增殖。已经确定了一个表位，这是承认的两头牛，我们假设，这些动物应该有共同的MHC II类等位基因。DRB 3、DQA和DQB等位基因的克隆和测序显示，这两种动物都具有DQA等位基因22021和DQB等位基因1301，但没有共同的DRB 3等位基因。一个平行的氨基酸残基参与MHC介绍肽丙氨酸取代的分析表明，在位置5和9的氨基酸残基内的十五肽代表的1A表位是重要的MHC结合在两个牛。这些数据表明，位于FMDV蛋白1A上的表位可以由DQA等位基因22021和DQB等位基因1301编码的MHC II类DQ分子呈递，并提供了该特定DQ分子结合基序的第一个证据。
Despite intensive research on the identification of T-cell epitopes in cattle after foot-and-mouth disease virus (FMDV) infection during the last 20 years, knowledge of major histocompatibility complex (MHC) restriction and anchor residues of such epitopes is still sparse. Therefore, as a first step, we tested lymphocytes from two experimentally FMDV serotype A24-vaccinated and -challenged cattle for recognition of FMDV-derived pentadecapeptides in proliferation assays. Two epitopes were identified: amino acid residues 66 to 80 within the structural protein 1D and amino acid residues 22 to 36 within the structural protein 1A. The latter epitope was recognized by lymphocytes from both cattle. Peptide-specific proliferation was caused by a response of CD4(+) T helper cells as identified by carboxyfluorescein diacetate succinimidyl ester proliferation assays. Having identified one epitope that was recognized by two cattle, we hypothesized that these animals should have common MHC class II alleles. Cloning and sequencing of DRB3, DQA, and DQB alleles revealed that both animals possessed DQA allele 22021 and DQB allele 1301 but had no common DRB3 allele. A parallel analysis of amino acid residues involved in MHC presentation by peptides with alanine substitutions showed that the amino acid residues in positions 5 and 9 within the pentadecapeptide representing the 1A epitope were important for MHC binding in both cattle. These data indicate that the epitope located on FMDV protein 1A can be presented by MHC class II DQ molecules encoded by DQA allele 22021 and DQB allele 1301 and present the first evidence of the binding motif of this particular DQ molecule.