Optimization of CD4+ T lymphocyte response to human cytomegalovirus nuclear IE1 protein through modifications of both size and cellular localization

Sandra Delmas, Laurence Martin, Michel Baron, Jay A. Nelson, Daniel N. Streblow, Jean Luc Davignon

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

We have previously reported that the CD4+ T lymphocyte response against nuclear human CMV IE1 protein depends in part on endogenous MHC class II presentation. To optimize presentation by HLA-DR of the nuclear IE1 protein and increase the response by CD4+ T cells, we have constructed two different adenovirus vectors containing mutant versions of IE1, containing a HLA-DR3 epitope, fused to GFP. The first construct consisted of a sequence of 46 aa encoded by exon 4, called GFP-IE1 (86-131). The second construct consisted of the whole IE1 mutated on exon 4 nuclear localization signals, identiied in this study, and deleted of already known exon 2 nuclear localization signals (GFP-IE1M). Both of these IE1 vectors expressed proteins with cytoplasmic localization, as evidenced by GFP expression, as opposed to control GFP-IE1, which was nuclear. GFP-IE1 (86-131) induced IE1-specific CD4+ T cell clone response that was >30-fold more potent than that against GFP-IE1 and GFP-IE1M. The CD4+ T cell response was due to endogenous presentation followed by exogenous presentation at later time points. Presentation was dependent on both proteasome and acidic compartments. GFP-IE1 (86-131) was rapidly degraded by the APC, which may account for better presentation. Our data show potentiation of the CD4+ T cell response to a specific epitope through shortening and relocation of an otherwise nuclear protein and suggest applications in vaccination.

Original languageEnglish (US)
Pages (from-to)6812-6819
Number of pages8
JournalJournal of Immunology
Volume175
Issue number10
DOIs
StatePublished - Nov 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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