THE CCR5 RECEPTOR ACTS AS AN ALLOANTIGEN IN CCR5-DELTA-32 HOMOZYGOUS INDIVIDUALS - IDENTIFICATION OF CHEMOKINE-BLOCKING AND HIV-1-BLOCKING HUMAN-ANTIBODIES

The chemokine receptor CCR5 is the major coreceptor for infection by m acrophage-tropic R5 HIV-1, A 32-bp deletion in the gene coding for CCR 5 (CCR5 Delta 32) occurs with a frequency of 10% in the Caucasian popu lation and results in a receptor protein that is truncated and not exp ressed at the cell surface. CCR5 Delta 32 homozygous individuals are a pparently normal but resistant to infection with R5 HIV-1, In two indi viduals homozygous for CCR5 Delta 32, who had been repeatedly exposed to CCR5-expressing blood cells through sexual activity, we have identi fied antibodies to CCR5 that bound specifically to the surface of CCR5 -expressing cell lines. Serum from these individuals, in contrast to s erum from CCR5(+/+) individuals, competed with radiolabeled RANTES for binding to the CCR5 receptor and inhibited infection of peripheral bl ood mononuclear cells with R5, but not X4, primary isolates of HIV-1, The identified human antibodies to CCR5 define an alloantigen that may cause allograft rejection in a mismatch situation even in individuals with no history of blood transfusions or i.v. drug abuse.