tetano
Editor, Senior Moderator
J Exp Med
. 2020 Oct 5;217(10):e20200206.
doi: 10.1084/jem.20200206.
Deciphering and Predicting CD4+ T Cell Immunodominance of Influenza Virus Hemagglutinin
Antonino Cassotta[SUP] 1 2 [/SUP], Philipp Paparoditis[SUP] 1 [/SUP], Roger Geiger[SUP] 1 [/SUP], Ramgopal R Mettu[SUP] 3 [/SUP], Samuel J Landry[SUP] 4 [/SUP], Alessia Donati[SUP] 1 [/SUP], Marco Benevento[SUP] 1 [/SUP], Mathilde Foglierini[SUP] 1 5 [/SUP], David J M Lewis[SUP] 6 [/SUP], Antonio Lanzavecchia[SUP] 1 [/SUP], Federica Sallusto[SUP] 1 2 [/SUP]
Affiliations
Abstract
The importance of CD4+ T helper (Th) cells is well appreciated in view of their essential role in the elicitation of antibody and cytotoxic T cell responses. However, the mechanisms that determine the selection of immunodominant epitopes within complex protein antigens remain elusive. Here, we used ex vivo stimulation of memory T cells and screening of naive and memory T cell libraries, combined with T cell cloning and TCR sequencing, to dissect the human naive and memory CD4+ T cell repertoire against the influenza pandemic H1 hemagglutinin (H1-HA). We found that naive CD4+ T cells have a broad repertoire, being able to recognize naturally processed as well as cryptic peptides spanning the whole H1-HA sequence. In contrast, memory Th cells were primarily directed against just a few immunodominant peptides that were readily detected by mass spectrometry-based MHC-II peptidomics and predicted by structural accessibility analysis. Collectively, these findings reveal the presence of a broad repertoire of naive T cells specific for cryptic H1-HA peptides and demonstrate that antigen processing represents a major constraint determining immunodominance.
. 2020 Oct 5;217(10):e20200206.
doi: 10.1084/jem.20200206.
Deciphering and Predicting CD4+ T Cell Immunodominance of Influenza Virus Hemagglutinin
Antonino Cassotta[SUP] 1 2 [/SUP], Philipp Paparoditis[SUP] 1 [/SUP], Roger Geiger[SUP] 1 [/SUP], Ramgopal R Mettu[SUP] 3 [/SUP], Samuel J Landry[SUP] 4 [/SUP], Alessia Donati[SUP] 1 [/SUP], Marco Benevento[SUP] 1 [/SUP], Mathilde Foglierini[SUP] 1 5 [/SUP], David J M Lewis[SUP] 6 [/SUP], Antonio Lanzavecchia[SUP] 1 [/SUP], Federica Sallusto[SUP] 1 2 [/SUP]
Affiliations
- PMID: 32644114
- DOI: 10.1084/jem.20200206
Abstract
The importance of CD4+ T helper (Th) cells is well appreciated in view of their essential role in the elicitation of antibody and cytotoxic T cell responses. However, the mechanisms that determine the selection of immunodominant epitopes within complex protein antigens remain elusive. Here, we used ex vivo stimulation of memory T cells and screening of naive and memory T cell libraries, combined with T cell cloning and TCR sequencing, to dissect the human naive and memory CD4+ T cell repertoire against the influenza pandemic H1 hemagglutinin (H1-HA). We found that naive CD4+ T cells have a broad repertoire, being able to recognize naturally processed as well as cryptic peptides spanning the whole H1-HA sequence. In contrast, memory Th cells were primarily directed against just a few immunodominant peptides that were readily detected by mass spectrometry-based MHC-II peptidomics and predicted by structural accessibility analysis. Collectively, these findings reveal the presence of a broad repertoire of naive T cells specific for cryptic H1-HA peptides and demonstrate that antigen processing represents a major constraint determining immunodominance.