IDENTIFICATION OF 2 CYTOTOXIC T-LYMPHOCYTE RECOGNIZED EPITOPES IN THE RAS PROTEIN

被引:83
|
作者
SKIPPER, J [1 ]
STAUSS, HJ [1 ]
机构
[1] UNIV COLL & MIDDLESEX SCH MED,COURTAULD INST BIOCHEM,IMPERIAL CANC RES FUND,LONDON W1P 8BT,ENGLAND
来源
JOURNAL OF EXPERIMENTAL MEDICINE | 1993年 / 177卷 / 05期
关键词
D O I
10.1084/jem.177.5.1493
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
We have investigated the possibility of inducing cytotoxic T lymphocytes (CTL) to Ras containing a mutation at position 61 or to normal Ras, using recombinant vaccinia viruses expressing these proteins. CTL from C57Bl/10 mice immunized with vaccinia expressing mutant Ras showed specificity for the mutant Ras protein and recognition of normal Ras was inefficient. The opposite specificity was observed after immunization with vaccinia expressing normal Ras, since CTL isolated from these mice recognized normal Ras well and mutant Ras inefficiently. Levels of endogenous Ras expression were insufficient for lysis by these CTL. One CTL epitope mapped to amino acids 60-67 and residue 61 was critical for T cell recognition. CTL generated against mutant Ras protein recognized peptide 60-67 containing mutant residue 61, while anti-normal Ras CTL recognized the wild-type 60-67 sequence. A second epitope mapped to residues 152-159 of Ras and was recognized equally well by CTL raised to normal or mutant Ras. The murine data raise the possibility of exploiting Ras-specific CTL for targeted immunotherapy of certain human cancers.
引用
收藏
页码:1493 / 1498
页数:6
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