tetano
Editor, Senior Moderator
J Virol. 2015 Jan 21. pii: JVI.03020-14. [Epub ahead of print]
[h=1]Narrowing of human influenza A virus specific T cell receptor α and β repertoire with increasing age.[/h] Gil A[SUP]1[/SUP], Yassai MB[SUP]2[/SUP], Naumov YN[SUP]1[/SUP], Selin LK[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Alterations in memory CD8 T cell responses may contribute to the high morbidity and mortality caused by seasonal influenza A virus (IAV) infections in older individuals. We questioned whether memory CD8 responses changed over time with increasing age to this non-persistent virus, to which recurrent exposure with new strains is common. Here, we show a direct correlation between increasing age and narrowing of the HLA-A2-restricted IAV M1 58-66: -specific Vα and Vβ T cell repertoires simultaneously leading to oligoclonal expansions including the usage of a single identical VA12-JA29 clonotype in all 8 older donors. The VA repertoire of older individuals also had longer CDR3 regions with increased usage of G/A runs, whose molecular flexibility may enhance TCR promiscuity. Collectively, these results suggest that CD8 memory T cell responses in humans to non-persistent viruses like IAV are dynamic, and with aging there is reduced diversity but preferential retention of T cell repertoires with features of enhanced cross-reactivity.
[h=4]IMPORTANCE:[/h] With increasing age the immune system undergoes drastic changes and older individuals have declined resistance to infections. Vaccinations become less effective and infection with influenza A virus in older individuals is associated with higher morbidity and mortality. Here, we questioned whether T cell responses directed against the highly conserved HLA-A2-restricted M1 58-66: peptide of IAV evolves with increasing age. Specifically, we postulated that CD8 T cell repertoires will narrow with recurrent exposure and thus may be less efficient in response to new infections with new strains of IAV. Detailed analyses of VA and VB TCR repertoire simultaneously showed a direct correlation between increasing age and narrowing of TCR repertoire. Features of the TCRs indicated potentially enhanced cross-reactivity in all older donors. In summary, T cell repertoire analysis in older individuals maybe useful as one of the predictors of protection after vaccination.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25609818 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25609818
[h=1]Narrowing of human influenza A virus specific T cell receptor α and β repertoire with increasing age.[/h] Gil A[SUP]1[/SUP], Yassai MB[SUP]2[/SUP], Naumov YN[SUP]1[/SUP], Selin LK[SUP]3[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] Alterations in memory CD8 T cell responses may contribute to the high morbidity and mortality caused by seasonal influenza A virus (IAV) infections in older individuals. We questioned whether memory CD8 responses changed over time with increasing age to this non-persistent virus, to which recurrent exposure with new strains is common. Here, we show a direct correlation between increasing age and narrowing of the HLA-A2-restricted IAV M1 58-66: -specific Vα and Vβ T cell repertoires simultaneously leading to oligoclonal expansions including the usage of a single identical VA12-JA29 clonotype in all 8 older donors. The VA repertoire of older individuals also had longer CDR3 regions with increased usage of G/A runs, whose molecular flexibility may enhance TCR promiscuity. Collectively, these results suggest that CD8 memory T cell responses in humans to non-persistent viruses like IAV are dynamic, and with aging there is reduced diversity but preferential retention of T cell repertoires with features of enhanced cross-reactivity.
[h=4]IMPORTANCE:[/h] With increasing age the immune system undergoes drastic changes and older individuals have declined resistance to infections. Vaccinations become less effective and infection with influenza A virus in older individuals is associated with higher morbidity and mortality. Here, we questioned whether T cell responses directed against the highly conserved HLA-A2-restricted M1 58-66: peptide of IAV evolves with increasing age. Specifically, we postulated that CD8 T cell repertoires will narrow with recurrent exposure and thus may be less efficient in response to new infections with new strains of IAV. Detailed analyses of VA and VB TCR repertoire simultaneously showed a direct correlation between increasing age and narrowing of TCR repertoire. Features of the TCRs indicated potentially enhanced cross-reactivity in all older donors. In summary, T cell repertoire analysis in older individuals maybe useful as one of the predictors of protection after vaccination.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.
PMID: 25609818 [PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25609818