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Post# of 148190
Of 10,000 hybridoma supernatants screened, well over 100 inhibited fusion by.50%, but only 6—designated PA8, PA9, PA10, PA11, PA12, and PA14.....
MAbs PA8 to PA12 and PA14 were initially selected on the basis of their ability to inhibit HIV-1 envelope-mediated membrane fusion.
In general, PA8 to PA12 were the most affected and PA14 and 2D7 were the least affected by this class of mutants,
MAbs PA14 and 2D7, however, blocked calcium mobilization induced by RANTES,
However, PA14and 2D7 stained the highest percentage of CD4+ lymphocytesand also yielded the highest MFI on these cells.
We favor the hypothesis that the coreceptor molecules present on L1.2-CCR51cells possess one HIV-1 entry-com-petent conformation whereas CCR5 molecules on PBMC,PM1, and CCR51U87MG exist in multiple entry-competent states that display different MAb reactivities. Whereas PA14and 2D7 may recognize all conformations, other MAbs may not.
Whereas 2D7 and RANTES binding maps primarily to ECL2, the PA14 epitopemaps to both ECL2 and the Nt domain and may have lesspotential for steric overlap. These data demonstrate the feasibility of developing chemokine receptor-specific HIV-1 inhibitors that do not block normal receptor activity, an observation with considerable therapeutic implications.