6nca: Difference between revisions
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/RTA_EBVG RTA_EBVG]] Immediate-early transcription factor that controls the initiation of viral lytic gene expression and lytic reactivation from latency. Triggers lytic replication, and initiates a cellular senescence program in epithelial cells. Upregulates human DCR3/TNFRSF6B by directly binding to its receptor (By similarity). [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. [[http://www.uniprot.org/uniprot/1A02_HUMAN 1A02_HUMAN]] Involved in the presentation of foreign antigens to the immune system. | [[http://www.uniprot.org/uniprot/RTA_EBVG RTA_EBVG]] Immediate-early transcription factor that controls the initiation of viral lytic gene expression and lytic reactivation from latency. Triggers lytic replication, and initiates a cellular senescence program in epithelial cells. Upregulates human DCR3/TNFRSF6B by directly binding to its receptor (By similarity). [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. [[http://www.uniprot.org/uniprot/1A02_HUMAN 1A02_HUMAN]] Involved in the presentation of foreign antigens to the immune system. | ||
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== Publication Abstract from PubMed == | |||
The T cell receptor (TCR) repertoire is an essential component of the CD8 T-cell immune response. Here, we seek to investigate factors that drive selection of TCR repertoires specific to the HLA-A2-restricted immunodominant epitope BRLF1109-117 (YVLDHLIVV) over the course of primary Epstein Barr virus (EBV) infection. Using single-cell paired TCRalphabeta sequencing of tetramer sorted CD8 T cells ex vivo, we show at the clonal level that recognition of the HLA-A2-restricted BRLF1 (YVL-BR, BRLF-1109) epitope is mainly driven by the TCRalpha chain. For the first time, we identify a CDR3alpha (complementarity determining region 3 alpha) motif, KDTDKL, resulting from an obligate AV8.1-AJ34 pairing that was shared by all four individuals studied. This observation coupled with the fact that this public AV8.1-KDTDKL-AJ34 TCR pairs with multiple different TCRbeta chains within the same donor (median 4; range: 1-9), suggests that there are some unique structural features of the interaction between the YVL-BR/MHC and the AV8.1-KDTDKL-AJ34 TCR that leads to this high level of selection. Newly developed TCR motif algorithms identified a lysine at position 1 of the CDR3alpha motif that is highly conserved and likely important for antigen recognition. Crystal structure analysis of the YVL-BR/HLA-A2 complex revealed that the MHC-bound peptide bulges at position 4, exposing a negatively charged aspartic acid that may interact with the positively charged lysine of CDR3alpha. TCR cloning and site-directed mutagenesis of the CDR3alpha lysine ablated YVL-BR-tetramer staining and substantially reduced CD69 upregulation on TCR mutant-transduced cells following antigen-specific stimulation. Reduced activation of T cells expressing this CDR3 motif was also observed following exposure to mutated (D4A) peptide. In summary, we show that a highly public TCR repertoire to an immunodominant epitope of a common human virus is almost completely selected on the basis of CDR3alpha and provide a likely structural basis for the selection. These studies emphasize the importance of examining TCRalpha, as well as TCRbeta, in understanding the CD8 T cell receptor repertoire. | |||
CDR3alpha drives selection of the immunodominant Epstein Barr virus (EBV) BRLF1-specific CD8 T cell receptor repertoire in primary infection.,Kamga L, Gil A, Song I, Brody R, Ghersi D, Aslan N, Stern LJ, Selin LK, Luzuriaga K PLoS Pathog. 2019 Nov 25;15(11):e1008122. doi: 10.1371/journal.ppat.1008122., eCollection 2019 Nov. PMID:31765434<ref>PMID:31765434</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
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== References == | == References == | ||
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