Document 0316
 DOCN  M9440316
 TI    Structure of the VH and VL segments of polyreactive and monoreactive
       human natural antibodies to HIV-1 and Escherichia coli
       beta-galactosidase.
 DT    9404
 AU    Harindranath N; Ikematsu H; Notkins AL; Casali P; Laboratory of Oral
       Medicine, National Institute of Dental; Research, National Institutes of
       Health, Bethesda, MD 20892.
 SO    Int Immunol. 1993 Dec;5(12):1523-33. Unique Identifier : AIDSLINE
       GENBANK/L25298
 AB    B lymphocytes committed to the production of antibodies binding to
       antigens on pathogenic bacteria and viruses (natural antibodies) are
       common components of the normal human B cell repertoire. A major
       proportion of natural antibodies is capable of binding multiple antigens
       (polyreactive antibodies). Using B cells from three HIV-1 seronegative
       healthy subjects, and purified HIV-1 and beta-galactosidase from
       Escherichia coli as selecting antigen, we generated three natural IgM
       mAb to HIV-1 and a natural IgM mAb to beta-galactosidase. The three
       HIV-1-selected antibodies (mAb102, mAb103, and mAb104) were
       polyreactive. They bound with different affinities (Kd = 10(-6) to
       10(-8) M) to the HIV-1 envelope gp160, the p24 core protein, and the p66
       reverse transcriptase, but not to the 120 glycosylated env protein. They
       also bound to beta-galactosidase (Kd approximately 10(-7) M), tetanus
       toxoid, and various various self antigens. In contrast, the natural mAb
       selected for binding to beta-galactosidase (mAb207.F1) was monoreactive,
       in that it bound with a high affinity (Kd < 10(-8) M) to this antigen,
       but to none of the other antigens tested, including HIV-1. Structural
       analysis of the VH and VL segments revealed that the natural mAb
       utilized three segments of the VHIV gene family and one of the VHIII
       family, in conjunction with VL segments of the V lambda I, V lambda II,
       V lambda III, or V kappa IV subgroups. In addition, the natural mAb VH
       and VL segments were in unmutated or virtually unmutated (germline)
       configuration, including those of the monoreactive mAb207.F1 to
       beta-galactosidase, and were identical or closely related to those
       utilized by specific autoantibodies or specific antibodies to viral
       and/or bacterial pathogens. Thus, the present data show that both
       polyreactive and monoreactive natural antibodies to foreign antigen can
       be isolated from the normal human B cell repertoire. They also suggest
       that the VH and VL segments of not only polyreactive but also
       monoreactive natural antibodies can be encoded in unmutated or minimally
       mutated genes, and possibly provide the templates for the specific high
       affinity antibodies elicited by self or foreign antigens.
 DE    beta-Galactosidase/*IMMUNOLOGY  Adult  Amino Acid Sequence  Antibodies,
       Bacterial/*CHEMISTRY/GENETICS  Antibodies, Monoclonal/CHEMISTRY/GENETICS
       B-Lymphocytes/IMMUNOLOGY  Base Sequence  Escherichia
       coli/ENZYMOLOGY/IMMUNOLOGY  Human  HIV Antibodies/*CHEMISTRY/GENETICS
       HIV-1/*IMMUNOLOGY  IgM/CHEMISTRY/GENETICS  Immunity, Natural
       Immunoglobulin Variable Region/*CHEMISTRY/GENETICS  Immunoglobulins,
       Heavy-Chain/GENETICS  Immunoglobulins, Light-Chain/CHEMISTRY/GENETICS
       Molecular Sequence Data  Support, U.S. Gov't, P.H.S.  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).