Dangers of restocking T cells

One person’s fight against an HIV infection can decrease the virus’s ability to threaten its next victim, say Goepfert et al. (page 1009). Mutations that help the virus survive in one host decrease its ability to replicate in the next. HIV mutations that help the virus bypass the host’s immune system often fall within gag. This gene is a favorite target for mutations because, for some reason, Gag epitopes that are presented by HLA B alleles create the most productive immune response. But Gag is also critical for viral replication. The infected individual doesn’t benefit from replicationdampening gag mutations, as the virus still escapes from cytotoxic T cells. Goepfert and colleagues now find, however, that the resulting decreased replication may benefit the patient’s sexual partner. Their study of 114 couples found that individuals who were infected by partners with certain HLA B alleles had much lower viral levels when more than five gag mutations were present. Viral levels were lowest in newly infected individuals who did not have the same type of HLA B alleles as their partners, perhaps because the recipients’ T cells efficiently targeted non-Gag epitopes of the mutated virus. At least five gag mutations were needed to reduce viral load significantly. This threshold might explain why a T cell vaccine that induces immune responses against two Gag epitopes failed in a recent trial. Better results might be gained by targeting more epitopes.