Herzig Carolyn T A, Mailloux Vanessa L, Baldwin Cynthia L
Department of Veterinary and Animal Sciences, University of Massachusetts, Integrated Sciences Building, 661 N. Pleasant St, Amherst, MA, 01003, USA.
Immunogenetics. 2015 Feb;67(2):95-109. doi: 10.1007/s00251-014-0817-y. Epub 2014 Dec 12.
Gamma delta T cells comprise the majority of blood T cells in ruminants at birth and remain at high levels for several years with most expressing the WC1 co-receptor. A subpopulation of Bos taurus WC1(+) cells expressing a restricted set of WC1 molecules respond immediately by proliferation and interferon-γ production to leptospira following vaccination, preceding the response by CD4 T cells. Our goal is to define the γδ T cell recognition elements involved. Previously, we showed that the responding cells employed a variety of TRDV genes indicating that the CDR1 and CDR2 of TCRδ could vary and may not be principally involved in antigen specificity. Murine and human γδ T cells bind T22 and self lipids through their CDR3δ. Like mice, cattle use up to five TRDD genes in a single CDR3δ adding flexibility to length and configuration for antigen binding. Here, we used spectratyping to evaluate the CDR3δ of leptospira-responsive cells. Little or no compartmentalization of CDR3δ was found for antigen-responsive cells that incorporated TRDV1, TRDV2, or TRDV3 even though they comprise the majority of the leptospira-responding population. Compartmentalization occurred for TRDV4-containing transcripts and was maintained over time and among cattle. However, no common amino acid motif was apparent in those CDR3δ sequences, although a bias in D gene usage occurred. We hypothesize that the restricted set of WC1 co-receptors expressed by the responding cells may lend specificity to the response through their ability to bind bacteria facilitating interaction of various TCRs with bacterial components resulting in cross-linking and activation.
γδ T细胞在反刍动物出生时构成血液中T细胞的大部分，并在几年内保持高水平，大多数表达WC1共受体。一小群表达有限数量WC1分子的牛WC1(+)细胞在接种疫苗后，会通过增殖和产生干扰素-γ对钩端螺旋体立即作出反应，早于CD4 T细胞的反应。我们的目标是确定所涉及的γδ T细胞识别元件。此前，我们表明反应细胞使用了多种TRDV基因，这表明TCRδ的CDR1和CDR2可能会有所不同，且可能并非主要参与抗原特异性。小鼠和人类的γδ T细胞通过其CDR3δ结合T22和自身脂质。与小鼠一样，牛在单个CDR3δ中使用多达五个TRDD基因，增加了抗原结合长度和构型的灵活性。在这里，我们使用光谱分型来评估钩端螺旋体反应细胞的CDR3δ。对于整合了TRDV1、TRDV2或TRDV3的抗原反应细胞，未发现CDR3δ有明显的分隔现象，尽管它们构成了钩端螺旋体反应群体的大部分。含有TRDV4的转录本出现了分隔现象，并且在不同时间和不同牛之间保持这种现象。然而，在那些CDR3δ序列中没有明显的共同氨基酸基序，尽管在D基因使用上存在偏差。我们假设反应细胞表达的有限数量的WC1共受体可能通过其结合细菌的能力赋予反应特异性，促进各种TCR与细菌成分的相互作用，从而导致交联和激活。
