title: Lymphocytic choriomeningitis virus infection yields overlapping CD4+ and CD8+ T-cell responses.
abstract: Activation of CD4(+) T cells helps establish and sustain other immune responses. We have previously shown that responses against a broad set of nine CD4(+) T-cell epitopes were present in the setting of lymphocytic choriomeningitis virus (LCMV) Armstrong infection in the context of H-2(d). This is quite disparate to the H-2(b) setting, where only two epitopes have been identified. We were interested in determining whether a broad set of responses was unique to H-2(d) or whether additional CD4(+) T-cell epitopes could be identified in the setting of the H-2(b) background. To pursue this question, we infected C57BL/6 mice with LCMV Armstrong and determined the repertoire of CD4(+) T-cell responses using overlapping 15-mer peptides corresponding to the LCMV Armstrong sequence. We confirmed positive responses by intracellular cytokine staining and major histocompatibility complex (MHC)-peptide binding assays. A broad repertoire of responses was identified, consisting of six epitopes. These epitopes originate from the nucleoprotein (NP) and glycoprotein (GP). Out of the six newly identified CD4(+) epitopes, four of them also stimulate CD8(+) T cells in a statistically significant manner. Furthermore, we assessed these CD4(+) T-cell responses during the memory phase of LCMV Armstrong infection and after infection with a chronic strain of LCMV and determined that a subset of the responses could be detected under these different conditions. This is the first example of a broad repertoire of shared epitopes between CD4(+) and CD8(+) T cells in the context of viral infection. These findings demonstrate that immunodominance is a complex phenomenon in the context of helper responses.
authors.affiliation: The La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
authors.forename: Courtney
authors.initials: C
authors.lastname: Dow
authors.forename: Carla
authors.initials: C
authors.lastname: Oseroff
authors.forename: Bjoern
authors.initials: B
authors.lastname: Peters
authors.forename: Courtney
authors.initials: C
authors.lastname: Nance-Sotelo
authors.forename: John
authors.initials: J
authors.lastname: Sidney
authors.forename: Michael
authors.initials: M
authors.lastname: Buchmeier
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sette
authors.forename: Bianca R
authors.initials: BR
authors.lastname: Mothé
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens / Q000378:metabolism; D007371:Interferon-gamma / Q000096:biosynthesis; D008216:Lymphocytic Choriomeningitis / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data
chemical_list: D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D007371:Interferon-gamma