Papadopoulos K P, Hesdorffer C S, Suciu-Foca N, Hibshoosh H, Harris P E
Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
Clin Cancer Res. 1999 Aug;5(8):2089-93.
To broaden the clinical applicability of peptide-based immunotherapy in breast cancer, there is a need to identify further tumor-associated peptide epitopes that are specific for HLA alleles, in addition to HLA-A2. The HLA-B44 haplotype is one of the most common HLA-B haplotypes, occurring in 10-20% of the population. We performed the structural characterization of HLA class I-bound self-peptides presented by a human breast cancer cell line with a HLA-A68, A32, B40, B44 haplotype, to identify potential tumor-specific antigens. Of 13 sequenced peptides, 1 peptide had the HLA-A68 peptide binding motif and 12 peptides had the HLA-B40, B44 peptide binding motif. One of the latter peptides, FEVRVCACPG, shared 100% homology to residues 270-279 of wild-type P53 protein. Our study, thus, provides direct evidence for the natural processing and presentation of p53 epitope 270-279 by HLA-B40, B44-bearing human breast tumor cells. Epitopes spanning this region of P53 may have potential use for immunotherapy in patients expressing HLA-A2 and -B44 supertypes.
为了拓宽基于肽的免疫疗法在乳腺癌中的临床应用范围，除了HLA - A2之外，还需要鉴定更多针对HLA等位基因的肿瘤相关肽表位。HLA - B44单倍型是最常见的HLA - B单倍型之一，在10% - 20%的人群中出现。我们对具有HLA - A68、A32、B40、B44单倍型的人乳腺癌细胞系所呈递的HLA I类结合自身肽进行了结构表征，以鉴定潜在的肿瘤特异性抗原。在13个测序的肽中，1个肽具有HLA - A68肽结合基序，12个肽具有HLA - B40、B44肽结合基序。后一种肽中的一个，FEVRVCACPG，与野生型P53蛋白的270 - 279位残基具有100%的同源性。因此，我们的研究为携带HLA - B40、B44的人乳腺肿瘤细胞天然加工和呈递p53表位270 - 279提供了直接证据。跨越P53这一区域的表位可能对表达HLA - A2和 - B44超型的患者的免疫治疗具有潜在用途。
