Evidence for distinct contributions of heavy and light chains to restriction of antibody recognition of the HIV-1 principal neutralization determinant.
We have used phage Ab display technology to analyze two mAbs to HIV-1 envelope proteins gp120 and gp41. From the data obtained we are able to demonstrate that the recognition of the principal neutralization determinant of different strains of HIV-1 by neutralizing mAb M77 is restricted by its heavy and light chains in different ways. Native M77 is able to recognize and neutralize HIV-1 strain IIIB through binding to the gp120 V3 loop. M77 is unable to recognize strains of HIV-1 that differ on either the left or right side of the V3 loop tip. A chain-switched Fab fragment containing the M77 Fd fragment and a different light chain was able to recognize HIV-1 strains that differ from IIIB on the left side but not the right side of the V3 loop tip.
Watkins
B A
BA
Laboratory of Tumor Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Davis
A E
AE
Fiorentini
S
S
di Marzo Veronese
F
F
Reitz
M S
MS
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001483:Base Sequence; D003001:Cloning, Molecular; D005803:Genes, Immunoglobulin; D015483:HIV Antibodies / Q000737:chemistry*; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry; D007143:Immunoglobulin Heavy Chains / Q000737:chemistry*; D007147:Immunoglobulin Light Chains / Q000737:chemistry*; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid
D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D007140:Immunoglobulin Fab Fragments; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains