Hannestad K, Kristoffersen G, Briand J P
Eur J Immunol. 1986 Aug;16(8):889-93. doi: 10.1002/eji.1830160803.
In the present study we have investigated the structure of the helper T cell (Th)-defined idiotope (Id) of myeloma protein 315 lambda 2 light chain (lambda 2(315] in BALB/c (H-2d) mice which carry a high-responder immune response gene for this Id. Three peptides were synthesized which spanned the third hypervariable region (HV3) of lambda 2(315): peptides 88-99, 94-108 and 91-108. Only peptide 91-108 was capable of eliciting carrier-specific Th that recognized M315 or free lambda 2(315). These Th did not recognize lambda 2(5-7) chain which differs from lambda 2(315) at 4 positions in this region; these are Tyr94, Ser95, Thr96, Tyr98 for lambda 2(5-7) and Phe94, Arg95, Asn96, Phe98 for lambda 2(315). Immunization with peptide analogues revealed that substitution of Tyr for Phe94 was compatible with Id-lambda 2(315) mimicry, but substitution of Ser for Arg95 or Thr for Asn96 destroyed the Th-recognized Id. Furthermore, Th primed with lambda 2(5-7) chain did not cross-react with lambda 2T952; these lambda 2 chains only differ from each other at positions 98 and 99 at the V lambda 2-J lambda 2 junction. The data indicate that individual amino acids of short peptide segments are critical for Th-recognized Id of the lambda 2 HV3 loop and V lambda 2-J lambda 2 junction. Furthermore, the immunogenicity of a small peptide suggests that the carrier (lambda 2)-specific Th recognize Id that have been processed by antigen-presenting cells (APC). This implies the existence of two categories of "internal images" of foreign or of self antigens: (a) serologically defined and (b) T lymphocyte defined. We propose that as a rule, Id processing by APC, including B cells, destroys the first and reveals the second category. The possible physiological function of these Id-specific T cells in network interactions with B cells is discussed.
在本研究中，我们调查了携带针对骨髓瘤蛋白315λ2轻链（λ2(315)）高反应性免疫应答基因的BALB/c（H-2d）小鼠中辅助性T细胞（Th）定义的骨髓瘤蛋白315λ2轻链独特型（Id）的结构。合成了跨越λ2(315)第三个高变区（HV3）的三个肽段：肽段88 - 99、94 - 108和91 - 108。只有肽段91 - 108能够引发识别M315或游离λ2(315)的载体特异性Th细胞。这些Th细胞不识别在该区域与λ2(315)有4个位置差异的λ2(5 - 7)链；对于λ2(5 - 7)链，这些位置是Tyr94、Ser95、Thr96、Tyr98，而对于λ2(315)链则是Phe94、Arg95、Asn96、Phe98。用肽类似物免疫显示，用Tyr替代Phe94与Id - λ2(315)模拟兼容，但用Ser替代Arg95或用Thr替代Asn96会破坏Th细胞识别的Id。此外，用λ2(5 - 7)链致敏的Th细胞与λ2T952没有交叉反应；这些λ2链仅在Vλ2 - Jλ2连接区的98和99位彼此不同。数据表明，短肽段的单个氨基酸对于λ2 HV3环和Vλ2 - Jλ2连接区的Th细胞识别的Id至关重要。此外，小肽的免疫原性表明载体（λ2）特异性Th细胞识别已由抗原呈递细胞（APC）加工的Id。这意味着存在两类外来或自身抗原的“内影像”：（a）血清学定义的和（b）T淋巴细胞定义的。我们提出，通常，包括B细胞在内的APC对Id的加工会破坏第一类并揭示第二类。讨论了这些Id特异性T细胞在与B细胞的网络相互作用中的可能生理功能。
