Human monoclonal Fab fragments from a combinatorial library prepared from an individual with a low serum titer to a virus.
An IgG1k lambda Fab library was generated on the surface of phage beginning with bone marrow RNA from a healthy 22-year-old human donor. The donor had been immunized to measles in his early childhood but had only a low serum titer to a measles antigen preparation. The resulting library of approximately 10(7) clones was panned against the measles antigen preparation and three positive Fab-producing clones identified by ELISA. One of the Fabs was found to be specific to measles and to bind with high apparent affinity (10(8) M-1). The other two bind with lower affinity and show marked cross-reactivity with a number of other antigens. They possess heavy chains derived, with extensive somatic modification, from the single member gene family VH6. The study indicates that both high-affinity specific antibodies and lower affinity polyreactive antibodies can be derived from the library approach under appropriate conditions.
Department of Immunology, Scripps Research Institute, La Jolla, Ca 92037.
E
E
Bender
G R
GR
Pilkington
D R
DR
Burton
D000328:Adult; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000235:genetics; D000915:Antibody Affinity; D000956:Antigens, Viral; D001402:B-Lymphocytes / Q000276:immunology; D003001:Cloning, Molecular; D015698:Genomic Library; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000096:biosynthesis* / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008458:Measles Vaccine / Q000276:immunology; D008459:Measles virus / Q000276:immunology*; D008969:Molecular Sequence Data
D000911:Antibodies, Monoclonal; D000914:Antibodies, Viral; D000956:Antigens, Viral; D007140:Immunoglobulin Fab Fragments; D007135:Immunoglobulin Variable Region; D008458:Measles Vaccine