Lymphocytic choriomeningitis virus infection yields overlapping CD4+ and CD8+ T-cell responses.
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.
Dow
Courtney
C
The La Jolla Institute for Allergy and Immunology, La Jolla, California 92037, USA.
Oseroff
Carla
C
Peters
Bjoern
B
Nance-Sotelo
Courtney
C
Sidney
John
J
Buchmeier
Michael
M
Sette
Alessandro
A
Mothé
Bianca R
BR
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
D018984:Epitopes, T-Lymphocyte; D006183:H-2 Antigens; D007371:Interferon-gamma