Apostolopoulos V, Lofthouse S A, Popovski V, Chelvanayagam G, Sandrin M S, McKenzie I F
Austin Research Institute, Heidelberg, Victoria, Australia.
Nat Biotechnol. 1998 Mar;16(3):276-80. doi: 10.1038/nbt0398-276.
The ability to mimic peptide/peptide and/or peptide/carbohydrate structures may be important in generating cross-reactive antibodies for autoimmune and other diseases. We show that the peptide sequence DAHWESWL can mimic the conformation of the unrelated MUC1 peptide SAPDTRPAP(G). Mice immunized with mannan-MUC1-peptides make cytotoxic T lymphocytes (CTLs) and are protected from MUC1+ tumors. We show that the same specific anti-MUC1 responses can be produced by immunizing with the DAHWESWL peptide; furthermore, specific tumor protection is obtained in a manner similar to that with MUC1 immunization. The DAHWESWL peptide immunization leads to CTLs that recognize H2Dd and H2Ld but not H2b or human leukocyte antigens-group A (HLA-A) 0201 presented MUC1 peptides. However, mutation of the DAHWESWL peptide to a more HLA-A0201-compatible structure with appropriate anchors (DLHWASWV), leads to the production of CTLs in HLA-A*0201 mice.
模拟肽/肽和/或肽/碳水化合物结构的能力对于产生针对自身免疫性疾病和其他疾病的交叉反应性抗体可能很重要。我们发现肽序列DAHWESWL可以模拟不相关的MUC1肽SAPDTRPAP(G)的构象。用甘露聚糖-MUC1-肽免疫的小鼠会产生细胞毒性T淋巴细胞（CTL），并受到MUC1+肿瘤的保护。我们表明，用DAHWESWL肽免疫也能产生相同的特异性抗MUC1反应；此外，以类似于MUC1免疫的方式获得了特异性肿瘤保护。用DAHWESWL肽免疫会导致CTL识别H2Dd和H2Ld，但不识别H2b或呈递MUC1肽的人类白细胞抗原A组（HLA-A）0201。然而，将DAHWESWL肽突变为具有适当锚定的更兼容HLA-A0201的结构（DLHWASWV），会在HLA-A*0201小鼠中产生CTL。
