A novel T-cell receptor mimic defines dendritic cells that present an immunodominant West Nile virus epitope in mice.
We used a newly generated T-cell receptor mimic monoclonal antibody (TCRm MAb) that recognizes a known nonself immunodominant peptide epitope from West Nile virus (WNV) NS4B protein to investigate epitope presentation after virus infection in C57BL/6 mice. Previous studies suggested that peptides of different length, either SSVWNATTAI (10-mer) or SSVWNATTA (9-mer) in complex with class I MHC antigen H-2D(b) , were immunodominant after WNV infection. Our data establish that both peptides are presented on the cell surface after WNV infection and that CD8(+) T cells can detect 10- and 9-mer length variants similarly. This result varies from the idea that a given T-cell receptor (TCR) prefers a single peptide length bound to its cognate class I MHC. In separate WNV infection studies with the TCRm MAb, we show that in vivo the 10-mer was presented on the surface of uninfected and infected CD8α(+) CD11c(+) dendritic cells, which suggests the use of direct and cross-presentation pathways. In contrast, CD11b(+) CD11c(-) cells bound the TCRm MAb only when they were infected. Our study demonstrates that TCR recognition of peptides is not limited to certain peptide lengths and that TCRm MAbs can be used to dissect the cell-type specific mechanisms of antigen presentation in vivo.
Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO, USA.
Sojung
S
Kim
Amelia K
AK
Pinto
Nancy B
NB
Myers
Oriana
O
Hawkins
Krysten
K
Doll
Saghar
S
Kaabinejadian
Jason
J
Netland
Michael J
MJ
Bevan
Jon A
JA
Weidanz
William H
WH
Hildebrand
Michael S
MS
Diamond
Ted H
TH
Hansen
D000818:Animals; D039481:CD11b Antigen / Q000032:analysis; D039521:CD11c Antigen / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D016056:Immunodominant Epitopes; D051379:Mice; D008810:Mice, Inbred C57BL; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000276:immunology; D014902:West Nile virus / Q000276:immunology*
D039481:CD11b Antigen; D039521:CD11c Antigen; D016056:Immunodominant Epitopes; C080107:NS4B protein, flavivirus; D011948:Receptors, Antigen, T-Cell; D017361:Viral Nonstructural Proteins
Antigen presentation; Cytotoxic T lymphocytes; Flavivirus; T-cell receptor mimic