Isolation of human antibody repertoires with preservation of the natural heavy and light chain pairing

被引:99
作者
Meijer, PJ [1 ]
Andersen, PS [1 ]
Hansen, MH [1 ]
Steinaa, L [1 ]
Jensen, A [1 ]
Lantto, J [1 ]
Oleksiewicz, MB [1 ]
Tengbjerg, K [1 ]
Poulsen, TR [1 ]
Coljee, VW [1 ]
Bregenholt, S [1 ]
Haurum, JS [1 ]
Nielsen, LS [1 ]
机构
[1] Symphogen AS, DK-2800 Lyngby, Denmark
关键词
antibody; human; antibody repertoire; cognate pairs; PCR;
D O I
10.1016/j.jmb.2006.02.040
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The humoral immune system in higher vertebrates is unique in its ability to generate highly diverse antibody responses against most pathogens as well as against certain malignancies. Several technologies have been developed to exploit this vast source of potentially therapeutic antibodies, including hybridoma technology, phage display and yeast display. Here, we present a novel, high-throughput technology (the Symplex Technology) for rapid direct cloning and identification of human antigen-specific high-affinity antibodies from single antibody-producing cells of immune individuals. The utility of the technology was demonstrated by isolation of diverse sets of unique high-affinity antibodies against tetanus toxoid and influenza virus from immunized volunteers. Hence, the Symplex Technology is a new method for the rapid isolation of high-affinity antibodies directly from humans. (c) 2006 Elsevier Ltd. All rights reserved.
引用
收藏
页码:764 / 772
页数:9
相关论文
共 18 条
  • [1] [Anonymous], ANTIBODY ENG PRACTIC
  • [2] A novel strategy for generating monoclonal antibodies from single, isolated lymphocytes producing antibodies of defined specificities
    Babcook, JS
    Leslie, KB
    Olsen, OA
    Salmon, RA
    Schrader, JW
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (15) : 7843 - 7848
  • [3] Yeast surface display for screening combinatorial polypeptide libraries
    Boder, ET
    Wittrup, KD
    [J]. NATURE BIOTECHNOLOGY, 1997, 15 (06) : 553 - 557
  • [4] Therapeutic antibodies for human diseases at the dawn of the twenty-first century
    Brekke, OH
    Sandlie, I
    [J]. NATURE REVIEWS DRUG DISCOVERY, 2003, 2 (01) : 52 - 62
  • [5] MAKING ANTIBODY FRAGMENTS USING PHAGE DISPLAY LIBRARIES
    CLACKSON, T
    HOOGENBOOM, HR
    GRIFFITHS, AD
    WINTER, G
    [J]. NATURE, 1991, 352 (6336) : 624 - 628
  • [6] ACTIVATION OF HUMAN PERIPHERAL-BLOOD B-CELLS FOLLOWING IMMUNIZATION WITH HEPATITIS-B SURFACE-ANTIGEN VACCINE
    CUPPS, TR
    GOLDSMITH, PK
    VOLKMAN, DJ
    GERIN, JL
    PURCELL, RH
    FAUCI, AS
    [J]. CELLULAR IMMUNOLOGY, 1984, 86 (01) : 145 - 154
  • [7] A large non-immunized human Fab fragment phage library that permits rapid isolation and kinetic analysis of high affinity antibodies
    de Haard, HJ
    van Neer, N
    Reurs, A
    Hufton, SE
    Roovers, RC
    Henderikx, P
    de Bruïne, AP
    Arends, JW
    Hoogenboom, HR
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (26) : 18218 - 18230
  • [8] A bidirectional phage display vector for the selection and mass transfer of polyclonal antibody libraries
    Den, W
    Sompuram, SR
    Sarantopoulos, S
    Sharon, J
    [J]. JOURNAL OF IMMUNOLOGICAL METHODS, 1999, 222 (1-2) : 45 - 57
  • [9] IN-CELL PCR FROM MESSENGER-RNA - AMPLIFYING AND LINKING THE REARRANGED IMMUNOGLOBULIN HEAVY AND LIGHT CHAIN V-GENES WITHIN SINGLE CELLS
    EMBLETON, MJ
    GOROCHOV, G
    JONES, PT
    WINTER, G
    [J]. NUCLEIC ACIDS RESEARCH, 1992, 20 (15) : 3831 - 3837
  • [10] ENGINEERING HYBRID GENES WITHOUT THE USE OF RESTRICTION ENZYMES - GENE-SPLICING BY OVERLAP EXTENSION
    HORTON, RM
    HUNT, HD
    HO, SN
    PULLEN, JK
    PEASE, LR
    [J]. GENE, 1989, 77 (01) : 61 - 68