The CCR5 receptor acts as an alloantigen in CCR5Δ32 homozygous individuals: Identification of chemokineand HIV-1-blocking human antibodies

The chemokine receptor CCR5 is the major coreceptor for infection by macrophage-tropic R5 HIV-1. A 32-bp deletion in the gene coding for CCR5 (CCR5Δ32) occurs with a frequency of 10% in the Caucasian population and results in a receptor protein that is truncated and not expressed at the cell surface. CCR5Δ32 homozygous individuals are apparently normal but resistant to infection with R5 HIV-1. In two individuals homozygous for CCR5Δ32, who had been repeatedly exposed to CCR5-expressing blood cells through sexual activity, we have identified antibodies to CCR5 that bound specifically to the surface of CCR5-expressing cell lines. Serum from these individuals, in contrast to serum from CCR5(+/+) individuals, competed with radiolabeled RANTES for binding to the CCR5 receptor and inhibited infection of peripheral blood 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.

趋化因子受体CCR5（chemokine receptor CCR5）是嗜巨噬细胞R5型人类免疫缺陷病毒1型（macrophage-tropic R5 HIV-1）感染的主要共受体。编码CCR5的基因存在32碱基对（32-bp）缺失变异（CCR5Δ32），该变异在高加索人群中的出现频率为10%，其编码的受体蛋白会发生截短且无法在细胞表面表达。CCR5Δ32纯合子个体表观表型正常，但可抵抗R5型HIV-1感染。在两名通过性接触反复暴露于表达CCR5血细胞的CCR5Δ32纯合子个体中，我们成功鉴定出可特异性结合表达CCR5的细胞系表面的抗CCR5抗体。与CCR5野生型（CCR5(+/+)）个体的血清相比，这两名个体的血清可竞争性抑制放射性标记的RANTES与CCR5受体的结合，并可抑制R5型（而非X4型）原代HIV-1分离株对外周血单个核细胞的感染。本次鉴定得到的抗CCR5人源抗体可界定一种同种抗原（alloantigen），即使在无输血史或静脉药物滥用史的个体中，该抗原也可能在同种移植配型不合的情况下引发移植排斥反应。