ANTIGENIC VARIATION IN GP120S FROM MOLECULAR CLONES OF HIV-1 LAI

To address the relationship between primary sequence variation in HIV- 1 gp120 and its antigenic structure in a simple system, we have measur ed the binding of human and murine monoclonal antibodies (MAbs) to gp1 20 from four molecular clones of HIV-1 LAI: HxB2, HxB3, Hx10, and NL4- 3. Despite the close relationship between these clones, and their rela tively conserved gp120 sequences, there is considerable variation in t heir antigenic structure, judged by MAb reactivities to the V2, V3, an d C4 domains and to discontinuous epitopes. Because of our prior studi es of the determinants of MAb binding to HxB2 gp120, we can make reaso nable estimates of how sequence variation among the LAI clone gp120s a ffects their binding of some MAbs; for other MAbs our current knowledg e of gp120 structure is too limited to allow such estimates. These res ults indicate that small variations in primary gp120 amino acid sequen ce can profoundly affect recognition of this glycoprotein by all five groups of defined anti-gp120 neutralizing antibodies.