Inhibition of T-cell responses by feeding peptides containing major and cryptic epitopes: studies with the Der p I allergen.
Inhibition of T-cell responses by feeding peptides containing major and cryptic epitopes: studies with the Der p I allergen.
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通过喂养含有主要和隐秘表位的肽来抑制 T 细胞反应：使用 Der p I 过敏原进行的研究。
作者：
G. Hoyne;M. Callow;M. Kuo;W. Thomas
H-2b小鼠通过产生对肽21-49、78-100、110-131和197-212中包含的优势表位致敏的T细胞来对222个残基的变应原Der p I作出应答。然而，用合成肽120-143和144-169进行免疫，揭示了隐蔽表位，其可以使T细胞对相应肽的应答敏感，并且如果将脾粘附细胞加入淋巴结培养物中，则可以使T细胞对整个过敏原敏感。结果表明，饲喂重组融合肽可显著抑制全抗原免疫小鼠的能力，如通过蛋白质或肽刺激的体外白细胞介素-2（IL-2）和粒细胞-巨噬细胞集落刺激因子（GM-CSF）/IL-3释放所测量的，尽管通过IL-2释放所测量的抑制更显著。这种抑制作用扩展到了除用于摄食的融合肽中的表位以外的表位。因此，喂食肽101-154抑制了对110-131和78-100的反应。融合肽1-14和188-222不抑制应答，尽管188-222确实含有表位。当给小鼠喂食含有隐蔽表位144-169的融合物时，也获得了抑制。含有隐蔽表位的肽抑制应答的能力对于基于肽的免疫治疗具有重要意义。
H-2b mice respond to the 222 residue allergen Der p I by producing T cells sensitized to the dominant epitopes encompassed in peptides 21-49, 78-100, 110-131 and 197-212. Immunization with the synthetic peptides 120-143 and 144-169, however, revealed cryptic epitopes which could sensitize T cells for responses to the respective peptides and, providing splenic adherent cells were added to lymph node cultures, to the whole allergen. It is shown that feeding recombinant fusion peptides can markedly inhibit the ability of the whole antigen to immunize mice, as measured by the in vitro interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF)/IL-3 release on stimulation with protein or peptides, although inhibition measured by IL-2 release was more marked. The inhibition extended to epitopes other than those in the fusion peptides used for feeding. Thus feeding peptide 101-154 inhibited responses to 110-131 and 78-100. Fusion peptides 1-14 and 188-222 did not inhibit responses, although 188-222 did contain an epitope. Inhibition was also obtained when mice were fed a fusion containing the cryptic epitope 144-169. The ability of peptides containing the cryptic epitopes to inhibit responses has significant implications for peptide-based immunotherapy.