Characterization of CD4+ T helper cell fine specificity to the envelope glycoproteins of simian immunodeficiency virus

Virus-specific CD4+ T cells (Th) play a crucial role in the control of lentiviral replication. To better understand the epitope-specificity of CD4+ Th repertoire to the envelope glycoprotein (Env) of simian immunodeficiency virus (SIV), we analyzed Th responses to 20-mer overlapping Env peptides in eight genetically heterogeneous macaques chronically infected with live attenuated SIV. A set of 19 'broadly reactive' Th peptide-epitopes was defined from the distinct sets of responder peptides for individual macaques. The majority of broadly reactive peptide-epitopes (14 of 19) were uniformly distributed on the transmembrane (TM) domain of Env. Only five broadly reactive responder peptides localized to the surface domain (SU) of Env, and they were all confined to two non-glycosylated regions towards its carboxyl-terminus. This first comprehensive report of Env peptide-specific Th responses associated with attenuated SIV vaccine immunity indicates a profound influence of glycosylation on the development of Th responses and has important implications for acquired immunodeficiency syndrome (AIDS) vaccine development.