Presentation of out-of-frame peptide MHC class I complexes by a novel translation initiation mechanism

被引:97
作者
Malarkannan, S
Horng, T
Shih, PP
Schwab, S
Shastri, N [1 ]
机构
[1] Univ Calif Berkeley, Dept Mol & Cell Biol, Div Immunol, Berkeley, CA 94720 USA
[2] Univ Calif Berkeley, Energy & Resources Grp, Berkeley, CA 94720 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S1074-7613(00)80067-9
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Immune surveillance by CD8 T cells requires that peptides derived from intracellular proteins be presented by MHC class I molecules on the target cell surface. Interestingly, MHC molecules can also present peptides encoded in alternate translational reading frames, some even without conventional AUG initiation codons. Using T cells to measure expression of MHC bound peptides, we identified the non-AUG translation initiation codons and established that their activity was at the level of translational rather than DNA replication or transcription mechanisms. This translation mechanism decoded the CUG initiation codon not as the canonical methionine but as the leucine residue, and its activity was independent of upstream translation initiation events. Naturally processed peptide/MHC complexes can thus arise from "noncoding" mRNAs via a novel translation initiation mechanism.
引用
收藏
页码:681 / 690
页数:10
相关论文
共 48 条
[1]   POSITION-+5 AND POSITION-+6 CAN BE MAJOR DETERMINANTS OF THE EFFICIENCY OF NON-AUG INITIATION CODONS FOR PROTEIN-SYNTHESIS [J].
BOECK, R ;
KOLAKOFSKY, D .
EMBO JOURNAL, 1994, 13 (15) :3608-3617
[2]   T-CELL-RECOGNIZED ANTIGENIC PEPTIDES DERIVED FROM THE CELLULAR GENOME ARE NOT PROTEIN-DEGRADATION PRODUCTS BUT CAN BE GENERATED DIRECTLY BY TRANSCRIPTION AND TRANSLATION OF SHORT SUBGENIC REGIONS - A HYPOTHESIS [J].
BOON, T ;
VANPEL, A .
IMMUNOGENETICS, 1989, 29 (02) :75-79
[3]  
BOON T, 1989, COLD SH Q B, V54, P587
[4]   Ribosomal scanning past the primary initiation codon as a mechanism for expression of CTL epitopes encoded in alternative reading frames [J].
Bullock, TNJ ;
Eisenlohr, LC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 184 (04) :1319-1329
[5]   Initiation codon scanthrough versus termination codon readthrough demonstrates strong potential for major histocompatibility complex class I-restricted cryptic epitope expression [J].
Bullock, TNJ ;
Patterson, AE ;
Franlin, LL ;
Notidis, E ;
Eisenlohr, LC .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (07) :1051-1058
[6]   INITIATION OF PROTEIN-SYNTHESIS BY THE EUKARYOTIC TRANSLATIONAL APPARATUS ON CIRCULAR RNAS [J].
CHEN, CY ;
SARNOW, P .
SCIENCE, 1995, 268 (5209) :415-417
[7]   TRANSFER RNA(IMET) FUNCTIONS IN DIRECTING THE SCANNING RIBOSOME TO THE START SITE OF TRANSLATION [J].
CIGAN, AM ;
FENG, L ;
DONAHUE, TF .
SCIENCE, 1988, 242 (4875) :93-97
[8]   A human minor histocompatibility antigen specific for B cell acute lymphoblastic leukemia [J].
Dolstra, H ;
Fredrix, H ;
Maas, F ;
Coulie, PG ;
Brasseur, F ;
Mensink, E ;
Adema, GJ ;
de Witte, TM ;
Figdor, CG ;
van de Wiel-van Kemenade, E .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (02) :301-308
[9]   Initiation of protein synthesis in mammalian cells with codons other than AUG and amino acids other than methionine [J].
Drabkin, HJ ;
Rajbhandary, UL .
MOLECULAR AND CELLULAR BIOLOGY, 1998, 18 (09) :5140-5147
[10]   Recognition of out-of-frame major histocompatibility complex class I-restricted epitopes in vivo [J].
Elliott, T ;
Bodmer, H ;
Townsend, A .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1996, 26 (05) :1175-1179