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Glycoprotein B from strain 17 of herpes simplex virus type I contains an invariant chain homologous sequence that binds to MHC class II molecules
Author(s) -
Sievers Elisabeth,
Neumann Jürgen,
Raftery Martin,
SchÖnrich Günther,
EisHübinger Anna Maria,
Koch Norbert
Publication year - 2002
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2002.01472.x
Subject(s) - biology , antigen presentation , major histocompatibility complex , herpes simplex virus , peptide sequence , virology , human leukocyte antigen , mhc class i , antigen processing , microbiology and biotechnology , sequence motif , mhc class ii , virus , antigen , genetics , immune system , t cell , gene
Summary 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.