SYNTHETIC PEPTIDE LIBRARIES IN THE DETERMINATION OF T-CELL EPITOPES AND PEPTIDE BINDING-SPECIFICITY OF CLASS-I MOLECULES

被引:35
作者
SCHUMACHER, TNM
VANBLEEK, GM
HEEMELS, MT
DERES, K
LI, KW
IMARAI, M
VERNIE, LN
NATHENSON, SG
PLOEGH, HL
机构
[1] NETHERLANDS CANC INST,DEPT CELLULAR BIOCHEM,1066 CX AMSTERDAM,NETHERLANDS
[2] UNIV TUBINGEN,INST ORGAN CHEM,W-7400 TUBINGEN 1,GERMANY
[3] FREE UNIV AMSTERDAM,1007 MC AMSTERDAM,NETHERLANDS
[4] YESHIVA UNIV ALBERT EINSTEIN COLL MED,DEPT MICROBIOL & IMMUNOL,BRONX,NY 10461
关键词
D O I
10.1002/eji.1830220612
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Major histocompatibility complex (MHC) class I molecules combine with short peptides of defined length and sequence. Here we describe an approach that may be used in the analysis of peptide preference of different allelic MHC class I molecules, and in the determination of T cell epitopes. We produced synthetic "peptide libraries" of limited complexity by standard peptide chemistry. Using these peptide mixtures we show that H-2 K(b) molecules can accomodate both 8- and 9-residue peptides, whereas D(b) molecules are unable to combine with peptides shorter than 9 amino acids present in these libraries.When these peptide mixtures are used to provide "fingerprints" of D(b) molecules and mutants thereof, both loss and gain of the ability to combine with certain peptides is observed. For the K(bm1) mutant a strong influence of amino acid substitutions in class I molecules on the peptides selected is observed. In these synthetic peptide mixtures, the presence of a specific T cell epitope, known to be represented once, can be detected. This-approach may be extended to the identification of new T cell epitopes from larger peptide libraries.
引用
收藏
页码:1405 / 1412
页数:8
相关论文
共 26 条
[1]   THE BINDING-AFFINITY AND DISSOCIATION RATES OF PEPTIDES FOR CLASS-I MAJOR HISTOCOMPATIBILITY COMPLEX-MOLECULES [J].
CERUNDOLO, V ;
ELLIOTT, T ;
ELVIN, J ;
BASTIN, J ;
RAMMENSEE, HG ;
TOWNSEND, A .
EUROPEAN JOURNAL OF IMMUNOLOGY, 1991, 21 (09) :2069-2075
[2]   RANDOM PEPTIDE LIBRARIES - A SOURCE OF SPECIFIC PROTEIN-BINDING MOLECULES [J].
DEVLIN, JJ ;
PANGANIBAN, LC ;
DEVLIN, PE .
SCIENCE, 1990, 249 (4967) :404-406
[3]   ALLELE-SPECIFIC MOTIFS REVEALED BY SEQUENCING OF SELF-PEPTIDES ELUTED FROM MHC MOLECULES [J].
FALK, K ;
ROTZSCHKE, O ;
STEVANOVIC, S ;
JUNG, G ;
RAMMENSEE, HG .
NATURE, 1991, 351 (6324) :290-296
[4]   PEPTIDE-BINDING SPECIFICITY OF THE MOLECULAR CHAPERONE BIP [J].
FLYNN, GC ;
POHL, J ;
FLOCCO, MT ;
ROTHMAN, JE .
NATURE, 1991, 353 (6346) :726-730
[5]   LIGHT-DIRECTED, SPATIALLY ADDRESSABLE PARALLEL CHEMICAL SYNTHESIS [J].
FODOR, SPA ;
READ, JL ;
PIRRUNG, MC ;
STRYER, L ;
LU, AT ;
SOLAS, D .
SCIENCE, 1991, 251 (4995) :767-773
[6]  
GUIMEZANES A, 1992, IN PRESS EUR J IMMUN, V22
[7]   ISOLATION OF 12 MONOCLONAL ANTIBODIES AGAINST IA AND H-2-ANTIGENS - SEROLOGICAL CHARACTERIZATION AND REACTIVITY WITH LYMPHOCYTE-B AND LYMPHOCYTE-T [J].
HAMMERLING, GJ ;
HAMMERLING, U ;
LEMKE, H .
IMMUNOGENETICS, 1979, 8 (5-6) :433-445
[8]   PREPARATION OF IODINE-131 LABELLED HUMAN GROWTH HORMONE OF HIGH SPECIFIC ACTIVITY [J].
HUNTER, WM ;
GREENWOOD, FC .
NATURE, 1962, 194 (4827) :495-&
[9]   IDENTIFICATION OF SELF PEPTIDES BOUND TO PURIFIED HLA-B27 [J].
JARDETZKY, TS ;
LANE, WS ;
ROBINSON, RA ;
MADDEN, DR ;
WILEY, DC .
NATURE, 1991, 353 (6342) :326-329
[10]   ERADICATION OF ADENOVIRUS E1-INDUCED TUMORS BY E1A-SPECIFIC CYTO-TOXIC LYMPHOCYTES-T [J].
KAST, WM ;
OFFRINGA, R ;
PETERS, PJ ;
VOORDOUW, AC ;
MELOEN, RH ;
VANDEREB, AJ ;
MELIEF, CJM .
CELL, 1989, 59 (04) :603-614