Acute Epstein Barr virus-induced infectious mononucleosis leads to expansion of highly diverse CD8 T cell repertoires crossreactive with influenza A (HUM6P.249)
| Autor: | Anna Gil, Nuray Aslan, Rabi Mishra, Liisa Selin |
|---|---|
| Rok vydání: | 2015 |
| Předmět: | |
| Zdroj: | The Journal of Immunology. 194:190.8-190.8 |
| ISSN: | 1550-6606 0022-1767 |
| DOI: | 10.4049/jimmunol.194.supp.190.8 |
| Popis: | The competence of T cell responses predominantly depends on how efficient T cell receptors (TCRs) are at recognizing antigenic epitopes. We show here that during acute infectious mononucleosis (IM) there was an expansion of IAV-M1-specific memory cells that are crossreactive with both EBV-BMLF1 and EBV-BRLF1 double-tetramer+ cells directly ex-vivo in HLA-A2+ patients. These crossreactive populations expanded dramatically in culture. For instance, there were multiple crossreactive populations in the IAV-M1 stimulated line. We systematically examined the characteristics of these crossreactive populations and compared them to the cognate IAV-M1, EBV-BMLF and -BRLF1 populations using TCR deep sequencing and gene array analysis of tetramer sorted cells. Surprisingly, both crossreactive and non-crossreactive populations were highly polyclonal with 1500-3500 different VA and VB clonotypes. The dominant clonotypes differed between the different populations. However, there were overlaps in either VB or VA usage consistent with their ability to bind both ligands. In one patient the M1-specific response used was an unusual dominant VB and was identical with the BMLF1-specific VB (VB2J2.7) but they differed in VA with M1 using VA13J50.1 and BMLF1 VA 12.1J12.1. Immune response signatures from gene array differed between the crossreactive and non-crossreactive populations consistent with the concept that crossreactive TCR selection may play a role in disease outcome. (NIHAI49320). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|