Diversity of the class II (I-Ak/I-Ek)-restricted T cell repertoire for influenza hemagglutinin and antigenic drift. Six nonoverlapping epitopes on the HA1 subunit are defined by synthetic peptides.
Diversity of the class II (I-Ak/I-Ek)-restricted T cell repertoire for influenza hemagglutinin and antigenic drift. Six nonoverlapping epitopes on the HA1 subunit are defined by synthetic peptides.
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II类（I-AK/I-EK）限制性T细胞库的多样性，用于流感血凝素和抗原漂移。 HA1亚基上的六个非重叠表位是由合成肽定义的。
DOI：
10.1084/jem.170.2.383
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发表时间：
1989-08-01
影响因子：
15.3
通讯作者：
THOMAS, DB
中科院分区：
文献类型：
--
作者：
BURT, DS;MILLS, KHG;SKEHEL, JJ;THOMAS, DB
从感染了X31 （H3N2）流感病毒的CBA小鼠中获得的h -2k限制性T细胞克隆显示，使用合成肽识别病毒血凝素（HA）的HA1亚基内不同的非重叠序列。在HA1序列68 ~ 83、120 ~ 139和269 ~ 288中鉴定出3个i - ak限制性T细胞序列，在I-Ek分子背景下出现的2个识别位点被定位到HA1序列226 ~ 245和246 ~ 265。针对这些HA1区域的特异性T细胞克隆表现出不同的能力，以区分由于抗原漂移而在其HA分子内积累取代的自然变异病毒。识别HA1 226-245和HA1 246-265序列的克隆不能区分自然变异，而是集中在这些表位内的保守序列上。大多数T细胞克隆对氨基酸取代敏感，这些氨基酸取代的特征是在HA1亚基的三个主要抗原位点内发生抗原漂移；突变病毒HA1亚基内HA1残基78(V)/83(K)和275(D)/278(I)的替换分别与HA1 68- 83和HA1 269-288序列特异性T细胞克隆的增殖反应降低75%相关。此外，识别HA1 120-139的克隆对突变病毒HK/71无反应，这意味着HA1序列中129(G)和/或132(Q)位置的氨基酸对识别至关重要。我们的数据，连同之前发现的序列HA1 53-63也是一个主要的i - ak限制性T细胞识别位点，证明了流感HA的T细胞识别水平的多样性，在单个小鼠单倍型中迄今未被识别，并暗示T细胞库对抗外来抗原的多样性可能比之前假设的要大。此外，HA特异性T细胞集中于HA的HA1亚基内的氨基酸的频率也具有抗原漂移的特征，这表明MHC ii类限制性T细胞无法识别突变HA分子内的特定表位，这可能对变型流感病毒逃避免疫识别的能力有重要贡献。
H-2k-restricted T cell clones derived from CBA mice infected with X31 (H3N2) influenza virus, were shown to recognize distinct, nonoverlapping sequences within the HA1 subunit of the viral hemagglutinin (HA) using synthetic peptides. Three I-Ak-restricted T cell sequences were identified within HA1 68-83, 120-139, and 269-288, and two recognition sites presented in the context of the I-Ek molecule were mapped to HA1 sequences 226-245 and 246-265. T cell clones specific for these regions of HA1 demonstrated varying abilities to differentiate between natural variant viruses that had accumulated substitutions within their HA molecules as a result of antigenic drift. Clones that recognized sequences HA1 226-245 and HA1 246-265 failed to discriminate between natural variants and focused on conserved sequences within these epitopes. A majority of T cell clones were sensitive to amino acid substitutions that have featured in antigenic drift occurring within three major antigenic sites of the HA1 subunit; substitutions at HA1 residues 78 (V)/83(K) and 275(D)/278(I) within the HA1 subunit of mutant viruses correlated with a 75% reduction in the proliferative response for T cell clones specific for sequences HA1 68- 83 and HA1 269-288, respectively. Furthermore, a clone that recognized HA1 120-139 was nonresponsive to a mutant virus HK/71, implicating amino acids at HA1 position 129(G) and/or 132(Q) within this sequence as crucial for recognition. Our data, together with the previous finding that sequence HA1 53-63 is also a major I-Ak-restricted T cell recognition site, demonstrate a level of diversity in the T cell recognition of influenza HA, within a single mouse haplotype hitherto unrecognized, and imply that the T cell repertoire diversity against foreign antigens may be greater than previously assumed. Furthermore, the frequency at which HA-specific T cells have been identified that focus on amino acids within the HA1 subunit of HA also featuring in antigenic drift, suggests that a failure of MHC class II-restricted T cells to recognize specific epitopes within mutant HA molecules may contribute significantly to the capacity of variant influenza viruses to evade immune recognition.
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影响因子：
64.5
作者：
BUUS, S;SETTE, A;GREY, HM
通讯作者：
GREY, HM
影响因子：
15.3
作者：
BRETT, SJ;CEASE, KB;BERZOFSKY, JA
通讯作者：
BERZOFSKY, JA
针对特异性的蛋白质小肽区域的T细胞克隆存在明显的识别表型。对主要的组织相容性抗原识别和免疫反应基因缺陷的克隆缺失模型的基础机制的影响。
DOI：
10.1084/jem.162.1.332
发表时间：
1985-07-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Shastri N;Oki A;Miller A;Sercarz EE
通讯作者：
Sercarz EE
DOI：
10.1073/pnas.82.6.1678
发表时间：
1985-01-01
影响因子：
11.1
作者：
FOLSOM, V;GAY, D;TONEGAWA, S
通讯作者：
TONEGAWA, S
影响因子：
11.4
作者：
ROTHBARD, JB;TAYLOR, WR
通讯作者：
TAYLOR, WR