The Cellular Localization of Human Cytomegalovirus Glycoprotein Expression Greatly Influences the Frequency and Functional Phenotype of Specific CD4+ T Cell Responses.
Bottom Line: In this study, we examine and contrast the magnitude and phenotype of the T cell immune response against gB, gH, and gL within healthy donors. gB-specific CD4(+) T cells were found in 95% of donors, and 29 epitopes were defined with gB-specific response sizes ranging from 0.02 to 2.88% of the CD4(+) T cell pool.Glycoproteins were effectively presented following delivery to APCs but only gB-derived epitopes were presented following endogenous synthesis. gB expression was observed exclusively within vesicular structures colocalizing with HLA-DM whereas gH was distributed evenly throughout the cytoplasm.These results reveal that gB is a uniquely immunogenic CMV glycoprotein and this is likely to reflect its unique pattern of endogenous Ag presentation.
Affiliation: School of Cancer Sciences, College of Medicine and Dentistry, University of Birmingham, Birmingham B15 2TT, United Kingdom; and email@example.com firstname.lastname@example.org.Show MeSH
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Mentions: gB-specific CD4+ T cells displayed a strongly cytotoxic phenotype (87% GzmB+) following peptide stimulation with very high levels of TNF-α and IFN-γ production (Fig. 3). Only 26% of responding cells expressed IL-2, although 16% exhibited a complete polyfunctional profile by expression of all four markers. In contrast, gH-specific T cells exhibited a markedly reduced cytotoxic profile, with GzmB expression observed in only 26% of cells, although it was noteworthy that 59% of gH-specific T cells retain the capacity to produce IL-2. T cell responses against the two gL-derived epitopes were comparable to those seen for gH-specific T cells (Fig. 3, bar charts).
Affiliation: School of Cancer Sciences, College of Medicine and Dentistry, University of Birmingham, Birmingham B15 2TT, United Kingdom; and email@example.com firstname.lastname@example.org.