Sequence and specificity analysis of recombinant human Fab anti-Rh D isolated by phage display

被引:26
作者
Miescher, S [1 ]
Vogel, M
Biaggi, C
Ramseyer, V
Hustinx, H
Eicher, N
Imboden, MA
Spycher, MO
Amstutz, H
Stadler, BM
机构
[1] Inselspital Bern, Inst Immunol & Allergy, CH-3010 Bern, Switzerland
[2] Inselspital Bern, ZLB Cent Lab, Blood Transfus Serv SRC, CH-3010 Bern, Switzerland
关键词
D O I
10.1046/j.1423-0410.1998.7540278.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background and Objectives: Hyperimmune anti-Rh D serum is worldwide in short supply. As a first step to develop an alternative source of Rh D antibodies, we describe in this study the isolation and characterization of recombinant anti-Rh D Fab fragments. Materials and Methods: Peripheral blood mononuclear cells harvested from a hyperimmunized donor were used to construct two combinatorial Fab libraries. Phages expressing these Fab fragments were selected on whole red blood cells followed by testing of positive clones in an indirect hemagglutination assay. Results: Individual Fab clones are of high affinity and competitively inhibit the binding of a registered anti-D immunoglobulin, The Fab clones are also specific against the partial D phenotypes, Rh33, D-III, D-IVa, D-IVb, D-Va, and D-VII. The 13 different but highly homologous clones express preferentially VH3 segments. Conclusion: These Fab fragments show potential for the development of a new generation of therapeutic anti-Rh D reagents.
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页码:278 / 287
页数:10
相关论文
共 45 条
[1]   HUMAN MONOCLONAL FAB FRAGMENTS DERIVED FROM A COMBINATORIAL LIBRARY BIND TO RESPIRATORY SYNCYTIAL VIRUS-F GLYCOPROTEIN AND NEUTRALIZE INFECTIVITY [J].
BARBAS, CF ;
CROWE, JE ;
CABABA, D ;
JONES, TM ;
ZEBEDEE, SL ;
MURPHY, BR ;
CHANOCK, RM ;
BURTON, DR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (21) :10164-10168
[2]  
Barbas CF., 1991, METHODS COMPANION ME, V2, P119
[3]  
Bender Eckhard, 1993, Human Antibodies and Hybridomas, V4, P74
[4]  
BLANCHER A, 1996, TRANSFUS CLIN BIOL, V36, P347
[5]   PRODUCTION OF HUMAN-IGM ANTI-D IN TISSUE-CULTURE BY EB-VIRUS-TRANSFORMED LYMPHOCYTES [J].
BOYLSTON, AW ;
GARDNER, B ;
ANDERSON, RL ;
HUGHESJONES, NC .
SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1980, 12 (04) :355-358
[6]   A LARGE ARRAY OF HUMAN MONOCLONAL-ANTIBODIES TO TYPE-1 HUMAN-IMMUNODEFICIENCY-VIRUS FROM COMBINATORIAL LIBRARIES OF ASYMPTOMATIC SEROPOSITIVE INDIVIDUALS [J].
BURTON, DR ;
BARBAS, CF ;
PERSSON, MAA ;
KOENIG, S ;
CHANOCK, RM ;
LERNER, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (22) :10134-10137
[7]   GERMLINE VARIABLE REGION GENE SEGMENT DERIVATION OF HUMAN MONOCLONAL ANTI-RH(D) ANTIBODIES - EVIDENCE FOR AFFINITY MATURATION BY SOMATIC HYPERMUTATION AND REPERTOIRE SHIFT [J].
BYE, JM ;
CARTER, C ;
CUI, YC ;
GORICK, BD ;
SONGSIVILAI, S ;
WINTER, G ;
HUGHESJONES, NC ;
MARKS, JD .
JOURNAL OF CLINICAL INVESTIGATION, 1992, 90 (06) :2481-2490
[8]   SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION [J].
CHOMCZYNSKI, P ;
SACCHI, N .
ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) :156-159
[9]  
CLARKE C A, 1963, Br Med J, V1, P979
[10]  
CRAWFORD DH, 1983, LANCET, V1, P386