Use of Transgenic HLA A∗0201/Kb and HHD II Mice To Evaluate Frequency of Cytomegalovirus IE1-Derived Peptide Usage in Eliciting Human CD8 Cytokine Response

Autor: Margaret C. Sanborn, Xiuli Li, Norma A. Lomeli, Maria C. Villacres, John A. Zaia, Ghislaine Gallez-Hawkins
Jazyk: angličtina
Rok vydání: 2003
Předmět:
Popis: Murine models to predict human cytomegalovirus (CMV) vaccine immunogenicity are available to detect the presence of a specific immune response, such as cytolytic T-lymphocyte (CTL) function (2, 5, 28), CD4+ gamma interferon (IFN-γ) helper response (15, 22), or antibody response to specific CMV proteins (18, 20, 21). Of interest is the use of the transgenic A2Kb mouse containing the human HLA A∗0201with the murine α3 chain (Kb) (9, 19, 29). The murine model HHD II is also a transgenic HLA A∗0201 mouse that contains a disrupted murine major histocompatibility complex (MHC) molecule, forcing the mouse to present all its immunological epitopes through the HLA pathway (10). Both have become useful models to investigate peptide recognition of specific proteins that can be extrapolated to human subjects. The immunodominant HLA A∗0201-restricted peptide (pp65495-503) of CMV pp65 has been well studied (3, 6, 12, 30), whereas there is no immunodominant peptide recognized for the CMV IE1 protein, despite the prevalence of an IE1-specific CTL response (11, 14, 16, 17). Three reports have described the stimulatory effect of peptides IE1p315-323, IE1p316-324, and IE1p354-362 from CMV IE1 in the context of HLA A∗0201 (11, 17, 24) in a cytokine flow cytometry or CTL assay. However, not all CMV-seropositive subjects respond to these peptides (17). This report describes the use of HLA A2 transgenic mice to identify a novel IE1 peptide, IE1-297, that is recognized by murine CTLs as well as human CD8 cells by cytokine flow cytometry.
Databáze: OpenAIRE