van Bergen J, Camps M, Offringa R, Melief C J, Ossendorp F, Koning F
Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, The Netherlands.
Cancer Res. 2000 Nov 15;60(22):6427-33.
Efficient loading of MHC class II molecules with a T helper epitope of choice can be achieved through genetic exchange of the MHC class II-associated invariant chain peptide (CLIP) sequence with a sequence encoding the helper peptide. We have now used this method to engineer a cellular vaccine that continuously expresses a tumor-specific helper epitope in a defined costimulatory context. We provide evidence (a) that this cellular vaccine induces peptide-specific helper T cells in vivo that are functional in protecting mice from challenge with a highly aggressive tumor, (b) that this vaccine can directly prime tumor-specific helper T cells in vivo, and (c) that this cellular vaccine is superior compared with similar cells loaded with synthetic T helper peptide in inducing tumor protection. In conclusion, cellular vaccines for activation of antigen-specific helper T cells can be greatly improved by the introduction of invariant chain constructs containing a T helper epitope by class II-associated invariant chain peptide exchange.
通过将MHC II类相关恒定链肽（CLIP）序列与编码辅助肽的序列进行基因交换，可实现用所选的T辅助表位有效加载MHC II类分子。我们现在已使用此方法构建一种细胞疫苗，该疫苗在确定的共刺激环境中持续表达肿瘤特异性辅助表位。我们提供的证据表明：（a）这种细胞疫苗在体内诱导出肽特异性辅助性T细胞，这些细胞在保护小鼠免受高侵袭性肿瘤攻击方面发挥作用；（b）这种疫苗可在体内直接启动肿瘤特异性辅助性T细胞；（c）与加载合成T辅助肽的类似细胞相比，这种细胞疫苗在诱导肿瘤保护方面更具优势。总之，通过II类相关恒定链肽交换引入含有T辅助表位的恒定链构建体，可极大地改进用于激活抗原特异性辅助性T细胞的细胞疫苗。
