Background: Sulfated tyrosines at the amino-terminus of the HIV-1 coreceptor CCR5 play an important role in the ability of CCR5 to support HIV-1 entry.

Method: Here we report that at least four antibodies that bind HIV-1 gp120 are tyrosine sulfated at the CDR3 loops of their respective heavy chains. These sulfate moieties are critical for their ability to associate with gp120. Binding of these antibodies to gp120 is enhanced by CD4 and competed by CCR5 and sulfated CCR5-derived peptides. These antibodies also preferentially bind gp120 of CCR5-using (R5) HIV-1 isolates. Therefore, they share a number of properties in common with CCR5. These data are the first to describe a functionally important modification of an antigen-binding domain of an antibody.

Conclusion: These antibodies are derived from individuals who effectively control HIV-1 replication, and they potently neutralize R5 isolates. Therefore, tyrosine sulfated anti-gp120 antibodies of this class may be useful in slowing or preventing infection.