Glycoprotein B from strain 17 of herpes simplex virus type I contains an invariant chain homologous sequence that binds to MHC class II molecules

Open Access
Publisher Website
Google Scholar
Abstract
Major histocompatibility complex class I (MHCI) molecules are major targets of virus evasion strategies because they introduce antigens from the biosynthesis pathway into the antigen‐processing and presentation pathways for immune recognition by CD8+ T cells. Little is known about viral strategies that interfere with the MHC class II (MHCII) antigen presentation pathway. We identified a six amino acid sequence from type I herpes simplex virus (HSV‐1) glycoprotein B (gB) that is identical to a sequence of human leucocyte antigen D (HLA‐D) ‐associated invariant chain (Ii). In addition, this gB sequence is adjacent to a highly conserved HLA‐DR1 binding motif. Both viral sequences together resemble the class II binding site of human Ii, consisting of a MHCII groove binding segment and a promiscuous binding site. We cloned gB from HSV‐1 strain 17 and demonstrate association of the virus envelope protein to three HLA‐DR allotypes. With chimeric Ii/gB fusion proteins we identified gB sequences that mediate promiscuous or allotype‐specific binding to the HLA‐DR peptide‐binding domain. Mutation of two Lys residues in the viral segment of Ii/gB abolished promiscuous binding to HLA‐DR heterodimers. The result indicates promiscuous binding of the virus sequence to HLA‐DR molecules and suggests a potential for HSV‐1 to manipulate antigen processing and presentation.