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.