TY - JOUR
T1 - Structure of the VH and VL segments of polyreactive and monoreactive human natural antibodies to HIV-1 and escherichia coli β-galactosidase
AU - Harindranath, Nagaradona
AU - Ikematsu, Hideyuki
AU - Notkins, Abner L.
AU - Casali, Paolo
N1 - Funding Information:
This work was supported in part by US Public Health Service grants AR-40908 and CA-16087 (15S1). This is publication no. 21 from the Jeanette Greenspan Laboratory for Cancer Research.
PY - 1993/12
Y1 - 1993/12
N2 - 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 β-galactosidase from Escherichia coli as selecting antigen, we generated three natural IgM mAb to HIV-1 and a natural IgM mAb to β-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 glycosilated env protein. They also bound to β-galactosidase (Kd̃10-7 M), tetanus toxoid, and various self antigens. In contrast, the natural mAb selected for binding to β-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 VλI, VλII, VλIII, or VxIV 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 β-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.
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 β-galactosidase from Escherichia coli as selecting antigen, we generated three natural IgM mAb to HIV-1 and a natural IgM mAb to β-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 glycosilated env protein. They also bound to β-galactosidase (Kd̃10-7 M), tetanus toxoid, and various self antigens. In contrast, the natural mAb selected for binding to β-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 VλI, VλII, VλIII, or VxIV 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 β-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.
KW - Complimentarity determining region
KW - Framework region
KW - Ig VH and VL segments
KW - Natural antibodies
KW - Polyreactivity
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U2 - 10.1093/intimm/5.12.1523
DO - 10.1093/intimm/5.12.1523
M3 - Article
C2 - 8312222
AN - SCOPUS:0027788044
VL - 5
SP - 1523
EP - 1533
JO - International Immunology
JF - International Immunology
SN - 0953-8178
IS - 12
ER -