Epitopes described in "Hierarchies in cytokine expression profiles for acute and resolving influenza virus-specific CD8+ T cell responses: correlation of cytokine profile and TCR avidity."

Article Authors:Nicole L La Gruta; Stephen J Turner; Peter C Doherty
Article Title:Hierarchies in cytokine expression profiles for acute and resolving influenza virus-specific CD8+ T cell responses: correlation of cytokine profile and TCR avidity.
Reference Detail
Reference ID:494
Abstract:The development and resolution phases of influenza-specific CD8(+) T cell cytokine responses to epitopes derived from the viral nucleoprotein (D(b)NP(366)) and acid polymerase (D(b)PA(224)) were characterized in C57BL/6J mice for a range of anatomical compartments in the virus-infected lung and lymphoid tissue. Lymphocyte numbers were measured by IFN-gamma expression following stimulation with peptide, while the quality of the response was determined by the intensity of staining and the distribution of CD8(+) T cells producing TNF-alpha and IL-2. Both the levels of expression and the prevalence of TNF-alpha(+) and IL-2(+) cells reflected the likely Ag load, with clear differences being identified for populations from the alveolar space vs the lung parenchyma. Irrespective of the site or time of T cell recovery, IL-2(+) cells were consistently found to be a subset of the TNF-alpha(+) population which was, in turn, contained within the IFN-gamma(+) set. The capacity to produce IL-2 may thus be considered to reflect maximum functional differentiation. The hierarchy in cytokine expression throughout the acute phase of the primary and secondary response tended to be D(b)PA(224) > D(b)NP(366). Both elution studies with the cognate tetramers and experiments measuring CD8 beta coreceptor dependence for peptide stimulation demonstrated the same D(b)PA(224) > D(b)NP(366) profile for TCR avidity. Overall, the quality of any virus-specific CD8(+) T cell response appears variously determined by the avidity of the TCR-pMHC interaction, the duration and intensity of Ag stimulation characteristic of the particular tissue environment, and the availability of CD4(+) T help.
Affiliations:Department of Microbiology and Immunology, University of Melbourne, Parkville, Vic., Australia. nllg@unimelb.edu.au
Reference Type:Literature
PubMed ID:15100298
Journal:J Immunol
Journal Volume:172
Article Pages:5553-60
Journal ISSN:0022-1767
Article Chemical List:Cytokines;Epitopes, T-Lymphocyte;Interleukin-2;PA protein, influenza viruses;Peptide Fragments;Receptors, Antigen, T-Cell;Tumor Necrosis Factor-alpha;Viral Core Proteins;Viral Proteins;nucleoprotein (366-374), influenza virus;Interferon-gamma;RNA Replicase
Article MeSH List:Acute Disease; Animals; Bronchoalveolar Lavage Fluid(cytology; immunology); CD8-Positive T-Lymphocytes(immunology; metabolism; virology); Cells, Cultured; Cytokines(biosynthesis); Dose-Response Relationship, Immunologic; Epitopes, T-Lymphocyte(immunology); Female; Influenza A virus(immunology); Interferon-gamma(biosynthesis); Interleukin-2(biosynthesis); Lung(immunology; metabolism); Lymphocyte Activation(genetics); Lymphocyte Count; Mice; Mice, Inbred C57BL; Mice, Knockout; Organ Specificity(immunology); Orthomyxoviridae Infections(genetics; immunology); Peptide Fragments(immunology); Protein Binding(immunology); RNA Replicase(immunology); Receptors, Antigen, T-Cell(metabolism); Tumor Necrosis Factor-alpha(biosynthesis); Viral Core Proteins(immunology); Viral Proteins(immunology)
Curation Last Updated:2016-01-08 20:02:40