title: Glycoprotein B from strain 17 of herpes simplex virus type I contains an invariant chain homologous sequence that binds to MHC class II molecules.
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.
authors.affiliation: Division of Immunobiology, Institute of Zoophysiology, University of Bonn, Germany.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Sievers
authors.forename: Jürgen
authors.initials: J
authors.lastname: Neumann
authors.forename: Martin
authors.initials: M
authors.lastname: Raftery
authors.forename: Günther
authors.initials: G
authors.lastname: SchOnrich
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Eis-Hübinger
authors.forename: Norbert
authors.initials: N
authors.lastname: Koch
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism*; D000956:Antigens, Viral / Q000378:metabolism; D001665:Binding Sites; D001667:Binding, Competitive; D019556:COS Cells; D006684:HLA-DR Antigens / Q000378:metabolism*; D018259:Herpesvirus 1, Human / Q000145:classification / Q000276:immunology / Q000378:metabolism*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017385:Sequence Homology; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*
chemical_list: D000944:Antigens, Differentiation, B-Lymphocyte; D000956:Antigens, Viral; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C040495:glycoprotein B, Simplexvirus; C045084:invariant chain