Antibody-mediated delivery of antigen to chemokine receptors on antigen-presenting cells results in enhanced CD4+ T cell responses

被引:20
作者
Schjetne, KW [1 ]
Gundersen, HT
Iversen, JG
Thompson, KM
Bogen, B
机构
[1] Univ Oslo, Rigshosp, Univ Hosp, Inst Immunol, N-0027 Oslo, Norway
[2] Univ Oslo, Inst Physiol, N-0316 Oslo, Norway
关键词
T cell; chemokine receptor; antigen presentation;
D O I
10.1002/eji.200324299
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Here, we have investigated if targeting of T cell epitopes to chemokine receptors results in improved CD4(+) T cell responses. Mouse monoclonal antibodies (mAb) with kappaL chains were targeted to various chemokine receptors expressed on human monocytes or immature dendritic cells (DC), and proliferation of cloned human, DR4-restricted CD4(+) T cells specific for mouse Ckappa(40-48) was measured. When using monocytes as antigen-presenting cells, mAb specific for CCR1, CCR2, CCR5, and CXCR4 were 100-10,000-fold more efficient at inducing T cell proliferation when compared to isotype-matched control mAb on a per molecule basis. Targeting of immature DC was less effective and was only seen with anti-CCR1 and anti-CXCR4 mAb. Anti-chemokine receptors mAb required to be processed by the conventional endosomal MHC class II presentation pathway. The mAb did not induce signaling through the chemokine receptors as they failed to induce mobilization of cytosolic Ca2+ and actin polymerization. They also failed to induce APC maturation. The results strongly suggest that chemokine receptors channel antigen into the endocytic pathway for presentation on MHC class II molecules. Targeting T cell epitopes to chemokine receptors by recombinant antibody should be a useful vaccine strategy for the induction of strong CD4(+) T cell responses.
引用
收藏
页码:3101 / 3108
页数:8
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