Immune proteins called HLA molecules help to activate killer T cell responses against pathogens. But according to a study that will be published online on December 14th in the Journal of Experimental Medicine (www.jem.org), one particular group of HLA molecules cripples this activation, perhaps explaining why HIV-infected individuals who express these HLAs progress to AIDS more rapidly than others.

AIDS develops more rapidly in individuals who express HLA B*35-Px than in those who express the highly related HLA B*35PY proteins. The new study, lead by Xu Yu at Massachusetts General Hospital, shows that B*35-Px molecules bind to and activate an inhibitory receptor on dendritic cells—cells that are needed to activate protective T cells. These findings suggest that inhibitory dendritic cell receptors should be taken into consideration during future efforts to design HIV-1 vaccines and therapies.