tetano
Editor, Senior Moderator
Nat Commun. 2019 Jun 28;10(1):2846. doi: 10.1038/s41467-019-10661-8.
Quantification of epitope abundance reveals the effect of direct and cross-presentation on influenza CTL responses.
Wu T[SUP]1[/SUP], Guan J[SUP]1[/SUP], Handel A[SUP]2[/SUP], Tscharke DC[SUP]3[/SUP], Sidney J[SUP]4[/SUP], Sette A[SUP]4,[/SUP][SUP]5[/SUP], Wakim LM[SUP]6[/SUP], Sng XYX[SUP]1[/SUP], Thomas PG[SUP]7[/SUP], Croft NP[SUP]8[/SUP], Purcell AW[SUP]9[/SUP], La Gruta NL[SUP]10,[/SUP][SUP]11[/SUP].
Author information
Abstract
The magnitude of T cell responses to infection is a function of the na?ve T cell repertoire combined with the context and duration of antigen presentation. Using mass spectrometry, we identify and quantify 21 class 1 MHC-restricted influenza A virus (IAV)-peptides following either direct or cross-presentation. All these peptides, including seven novel epitopes, elicit T cell responses in infected C57BL/6 mice. Directly presented IAV epitopes maintain their relative abundance across distinct cell types and reveal a broad range of epitope abundances. In contrast, cross-presented epitopes are more uniform in abundance. We observe a clear disparity in the abundance of the two key immunodominant IAV antigens, wherein direct infection drives optimal nucleoprotein (NP)[SUB]366-374[/SUB] presentation, while cross-presentation is optimal for acid polymerase (PA)[SUB]224-233[/SUB] presentation. The study demonstrates how assessment of epitope abundance in both modes of antigen presentation is necessary to fully understand the immunogenicity and response magnitude to T cell epitopes.
PMID: 31253788 PMCID: PMC6599079 DOI: 10.1038/s41467-019-10661-8
Free PMC Article
Quantification of epitope abundance reveals the effect of direct and cross-presentation on influenza CTL responses.
Wu T[SUP]1[/SUP], Guan J[SUP]1[/SUP], Handel A[SUP]2[/SUP], Tscharke DC[SUP]3[/SUP], Sidney J[SUP]4[/SUP], Sette A[SUP]4,[/SUP][SUP]5[/SUP], Wakim LM[SUP]6[/SUP], Sng XYX[SUP]1[/SUP], Thomas PG[SUP]7[/SUP], Croft NP[SUP]8[/SUP], Purcell AW[SUP]9[/SUP], La Gruta NL[SUP]10,[/SUP][SUP]11[/SUP].
Author information
Abstract
The magnitude of T cell responses to infection is a function of the na?ve T cell repertoire combined with the context and duration of antigen presentation. Using mass spectrometry, we identify and quantify 21 class 1 MHC-restricted influenza A virus (IAV)-peptides following either direct or cross-presentation. All these peptides, including seven novel epitopes, elicit T cell responses in infected C57BL/6 mice. Directly presented IAV epitopes maintain their relative abundance across distinct cell types and reveal a broad range of epitope abundances. In contrast, cross-presented epitopes are more uniform in abundance. We observe a clear disparity in the abundance of the two key immunodominant IAV antigens, wherein direct infection drives optimal nucleoprotein (NP)[SUB]366-374[/SUB] presentation, while cross-presentation is optimal for acid polymerase (PA)[SUB]224-233[/SUB] presentation. The study demonstrates how assessment of epitope abundance in both modes of antigen presentation is necessary to fully understand the immunogenicity and response magnitude to T cell epitopes.
PMID: 31253788 PMCID: PMC6599079 DOI: 10.1038/s41467-019-10661-8
Free PMC Article