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Virus‐encoded ectopic CD 74 enhances poxvirus vaccine efficacy
Author(s) -
Walline Crystal C.,
Deffit Sarah N.,
Wang Nan,
Guindon Lynette M.,
Crotzer Victoria L.,
Liu Jianyun,
Hollister Kristin,
Eisenlohr Laurence C.,
Brutkiewicz Randy R.,
Kaplan Mark H.,
Blum Janice S.
Publication year - 2014
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12210
Subject(s) - biology , virology , cd74 , mhc class i , antigen , virus , antigen presentation , mhc class ii , immunology , immune system , vaccinia , antigen processing , major histocompatibility complex , recombinant dna , t cell , genetics , gene
Summary Vaccinia virus (VV) has been used globally as a vaccine to eradicate smallpox. Widespread use of this viral vaccine has been tempered in recent years because of its immuno‐evasive properties, with restrictions prohibiting VV inoculation of individuals with immune deficiencies or atopic skin diseases. VV infection is known to perturb several pathways for immune recognition including MHC class II (MHCII) and CD1d‐restricted antigen presentation. MHCII and CD1d molecules associate with a conserved intracellular chaperone, CD74, also known as invariant chain. Upon VV infection, cellular CD74 levels are significantly reduced in antigen‐presenting cells, consistent with the observed destabilization of MHCII molecules. In the current study, the ability of sustained CD74 expression to overcome VV‐induced suppression of antigen presentation was investigated. Viral inhibition of MHCII antigen presentation could be partially ameliorated by ectopic expression of CD74 or by infection of cells with a recombinant VV encoding murine CD74 ( mCD 74‐VV). In contrast, virus‐induced disruptions in CD1d‐mediated antigen presentation persisted even with sustained CD74 expression. Mice immunized with the recombinant mCD 74‐VV displayed greater protection during VV challenge and more robust anti‐VV antibody responses. Together, these observations suggest that recombinant VV vaccines encoding CD74 may be useful tools to improve CD4 + T‐cell responses to viral and tumour antigens.