Schirmbeck R, Melber K, Kuhröber A, Janowicz Z A, Reimann J
Institute for Microbiology, University of Ulm, Germany.
J Immunol. 1994 Feb 1;152(3):1110-9.
Immunization with soluble proteins only rarely induces a specific response of CD8+ CTL. We describe experiments that demonstrate the efficient and specific in vivo priming of CTL in BALB/c mice immunized with soluble hepatitis B virus (HBV)-derived surface (S) protein. A single (s.c., i.p. or i.v.) injection of a low dose (30 ng to 3 micrograms per mouse) of recombinant S protein particles without adjuvants induced a CTL response. This specific cytotoxic response was read out against a panel of different S protein-expressing transfected mouse cell lines. Effector cells of this response were Ld-restricted, CD3+ CD4- CD8+ CTL. H-2d/Ld+ (BALB/c, C.B-17) mice were responders; H-2d/Ld- (dm2) mutant mice and H-2b (C57BL/6) mice were nonresponders. Injections of various dosages of a S protein-derived, immunogenic, synthetic peptide into BALB/c mice by various routes did not prime CTL. After incorporation of S protein particles into IFA or aluminum hydroxide, these protein Ag lost their ability to specifically stimulate CTL in vivo. After priming of mice with S protein emulsified in IFA or adsorbed to aluminum hydroxide boost injections with native S protein particles were inefficient in stimulating a specific CTL response. These findings are of relevance for the design of synthetic subunit vaccines for which specific stimulation of CD8+ T effector functions is desired.
仅用可溶性蛋白质进行免疫很少能诱导CD8 + CTL产生特异性反应。我们描述了一些实验，这些实验证明在用可溶性乙肝病毒（HBV）衍生的表面（S）蛋白免疫的BALB / c小鼠中，CTL在体内能被有效且特异地启动。单次（皮下、腹腔内或静脉内）注射低剂量（每只小鼠30 ng至3 μg）无佐剂的重组S蛋白颗粒可诱导CTL反应。针对一组不同的表达S蛋白的转染小鼠细胞系检测了这种特异性细胞毒性反应。该反应的效应细胞是受Ld限制的CD3 + CD4 - CD8 + CTL。H - 2d / Ld +（BALB / c，C.B - 17）小鼠有反应；H - 2d / Ld -（dm2）突变小鼠和H - 2b（C57BL / 6）小鼠无反应。通过各种途径向BALB / c小鼠注射不同剂量的S蛋白衍生的免疫原性合成肽均不能启动CTL。将S蛋白颗粒掺入IFA或氢氧化铝后，这些蛋白质抗原失去了在体内特异性刺激CTL的能力。在用IFA乳化或吸附于氢氧化铝的S蛋白对小鼠进行初次免疫后，用天然S蛋白颗粒进行加强注射在刺激特异性CTL反应方面效率不高。这些发现与期望特异性刺激CD8 + T效应功能的合成亚单位疫苗的设计相关。
