Lo-Man R, Martineau P, Hofnung M, Leclerc C
Unité de Biologie des Régulations Immunitaires, Institut Pasteur, Paris, France.
Cell Immunol. 1996 Sep 15;172(2):180-91. doi: 10.1006/cimm.1996.0231.
CD4+ T cell responses are restricted by MHC class II-encoded glycoproteins which display antigen-derived peptides. Chimeric MalE proteins expressing foreign T cell epitopes represent a potent means to induce immune responses for recombinant vaccine design. Here, we studied the influence of the non-MHC genetic background and of the processing heterogeneity displayed by various APC types on the presentation of these chimeric proteins to T cells. For this purpose, the I-Ed-restricted poliovirus CD4+ T cell epitope was inserted into five different positions on the surface of MalE protein and the immunogenicity of the recombined T cell epitope was determined in different inbred mice. Immunization of several mouse strains expressing I-Ed with these chimeric proteins induced poliovirus-specific T cell response with four out of five constructs. In vitro presentation studies of the recombined epitope to specific T cells indicated that for a given chimeric protein the fine processing is conserved, whatever the non-H-2 genetic background of APC or the type of APC. Our results show that the insertion site in MalE modulates the immunogenicity of the recombined T cell epitope, but this phenomenon is only related to the MHC genetic background.
CD4 + T细胞反应受主要组织相容性复合体（MHC）II类编码的糖蛋白限制，这些糖蛋白展示抗原衍生的肽段。表达外源T细胞表位的嵌合麦芽糖结合蛋白（MalE）是重组疫苗设计中诱导免疫反应的有效手段。在此，我们研究了非MHC遗传背景以及各种抗原呈递细胞（APC）类型所表现出的加工异质性对这些嵌合蛋白向T细胞呈递的影响。为此，将I-Ed限制性脊髓灰质炎病毒CD4 + T细胞表位插入MalE蛋白表面的五个不同位置，并在不同的近交系小鼠中测定重组T细胞表位的免疫原性。用这些嵌合蛋白免疫几种表达I-Ed的小鼠品系，五种构建体中有四种诱导了脊髓灰质炎病毒特异性T细胞反应。对重组表位与特异性T细胞进行的体外呈递研究表明，对于给定的嵌合蛋白，无论APC的非H-2遗传背景或APC类型如何，精细加工都是保守的。我们的结果表明，MalE中的插入位点调节重组T细胞表位的免疫原性，但这种现象仅与MHC遗传背景有关。
