LCMV gp33-41

LCMV gp33-41 is a 9-amino acid cytotoxic T lymphocyte (CTL) epitope derived from the glycoprotein GP1 of the Lymphocytic Choriomeningitis Virus (LCMV). LCMV gp33-41 mediates antiviral cellular immune responses by activating specific CD8⁺ cytotoxic T cells through H-2Db-restricted antigen presentation^[1-2]. LCMV gp33-41 can be utilized in research related to virus-specific T cell detection, investigation of immunological memory mechanisms, and the development of antiviral immunotherapy platforms^[3-4].

In vitro, TCR-transgenic splenocytes were treated with LCMV gp33-41 (5µM) for 2 hours, followed by stimulation with IL-2-containing medium for 5 days. LCMV gp33-41 successfully induced and expanded activated GP33-specific CD8⁺ T effector cells^[5]. Bone marrow-derived macrophages (BMDMs) were pulsed overnight with LCMV gp33-41 (10ng/µL) and LPS (100ng/mL), and subsequently co-cultured with P14 CD8⁺ T cells specific for this antigen for 3 days. LCMV gp33-41 induced the expression of the activation marker CD44 on T cells^[6].

In vivo, bone marrow-derived dendritic cells (BMDCs) were pulsed with the LCMV gp33-41 (1µM) for 1 hour. Subsequently, 100 to 1×10⁶ of these DCs were adoptively transferred into C57BL/6 mice via intravenous, subcutaneous, or direct intrasplenic injection. LCMV gp33-41 efficiently induced a virus-specific cytotoxic T lymphocyte (CTL) response, conferring rapid and long-term protection against LCMV challenge to the mice. LCMV gp33-41 also enabled the clearance of the virus from peripheral tissues (such as the ovaries and brain), thereby preventing lethal choriomeningitis^[7]. The LCMV gp33-41 (100µg) emulsified in complete Freund's adjuvant was used to subcutaneously prime C57BL/6 mice on day 0, followed by booster immunizations with the same dose of peptide emulsified in incomplete Freund's adjuvant on days 7 and 14. LCMV gp33-41 induced only a low frequency of specific CD8 T cells in mice. The majority of these cells exhibited an effector-like phenotype (CD127⁻CD62L⁻) and expressed the inhibitory receptor PD-1^[8].

References:
[1] Smyth M, Khamina K, Popa A, et al. Characterization of CD8 T Cell-Mediated Mutations in the Immunodominant Epitope GP33-41 of Lymphocytic Choriomeningitis Virus. Front Immunol. 2021 Jun 14;12:638485.
[2] Gairin JE, Mazarguil H, Hudrisier D, et al. Optimal lymphocytic choriomeningitis virus sequences restricted by H-2Db major histocompatibility complex class I molecules and presented to cytotoxic T lymphocytes. J Virol. 1995 Apr;69(4):2297-305.
[3] Fridkis-Hareli M, Reinherz EL. New approaches to eliciting protective immunity through T cell repertoire manipulation: the concept of thymic vaccination. Med Immunol. 2004 Dec 8;3(1):2.
[4] Gallimore A, Glithero A, Godkin A, et al. Induction and exhaustion of lymphocytic choriomeningitis virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class I-peptide complexes. J Exp Med. 1998 May 4;187(9):1383-93.
[5] Laidlaw BJ, Decman V, Ali MA, et al. Cooperativity between CD8+ T cells, non-neutralizing antibodies, and alveolar macrophages is important for heterosubtypic influenza virus immunity. PLoS Pathog. 2013 Mar;9(3):e1003207.
[6] Hering M, Madi A, Sandhoff R, et al. Sphinganine recruits TLR4 adaptors in macrophages and promotes inflammation in murine models of sepsis and melanoma. Nat Commun. 2024 Jul 18;15(1):6067.
[7] Ludewig B, Ehl S, Karrer U, et al. Dendritic cells efficiently induce protective antiviral immunity. J Virol. 1998 May;72(5):3812-8.
[8] Liu Y, Xu L, Jiang Y, et al. Phenotypic and functional analysis of LCMV gp33-41-specific CD8 T cells elicited by multiple peptide immunization in mice revealed the up-regulation of PD-1 expression on antigen-specific CD8 T cells. Cell Mol Immunol. 2007 Dec;4(6):431-7.

LCMV gp33-41是一种来源于淋巴细胞性脉络丛脑膜炎病毒（LCMV）糖蛋白GP1的9肽CTL表位，LCMV gp33-41可通过H-2Db限制性呈递激活特异性CD8⁺细胞毒性T细胞来介导抗病毒细胞免疫应答^[1-2]。LCMV gp33-41可用于病毒特异性T细胞检测、免疫记忆机制研究和抗病毒免疫治疗平台开发的相关研究^[3-4]。

在体外，LCMV gp33-41（5μM）处理TCR转基因脾细胞2小时，随后使用含有IL-2培养基刺激细胞5天。LCMV gp33-41成功诱导并扩增出活化的GP33特异性CD8+ T效应细胞^[5]。LCMV gp33-41（10ng/μL）与LPS（100ng/mL）脉冲处理骨髓来源巨噬细胞（BMDM）过夜，随后与能特异性识别该抗原的P14 CD8+ T细胞共培养3天。LCMV gp33-41可诱导T细胞上激活标志物CD44的表达^[6]。

在体内，LCMV gp33-41（1μM）脉冲负载骨髓来源的树突状细胞（BMDC）1小时，随后通过静脉注射、皮下注射或直接脾内注射，将100至1×10⁶个该DC过继转移给C57BL/6小鼠。该处理能高效诱导病毒特异性细胞毒性T淋巴细胞（CTL）反应，使小鼠获得针对淋巴细胞脉络丛脑膜炎病毒（LCMV）攻击的快速、长期保护，并能清除外周组织（如卵巢和大脑）中的病毒，从而避免致死性脉络丛脑膜炎^[7]。LCMV gp33-41（100μg）在完全弗氏佐剂中乳化后，于第0天对C57BL/6小鼠进行皮下注射初次免疫，并在第7天和第14天用不完全弗氏佐剂乳化相同剂量的肽段进行加强免疫。LCMV gp33-41在小鼠体内仅诱导出低频率的特异性CD8 T细胞，其中大部分细胞呈现效应样表型（CD127⁻CD62L⁻），并表达抑制性受体PD-1^[8]。