Visualizing CTL activity for different CD8+ effector T cells supports the idea that lower TCR/epitope avidity may be advantageous for target cell killing

Cell Death and Differentiation
M R JenkinsN J Waterhouse

Abstract

Time-lapse video microscopy allows analysis of the interaction between individual CTLs and adherent peptide-pulsed targets, from contact, to lymphocyte detachment, APC rounding, phosphatidylserine exposure and finally loss of plasma membrane integrity characteristic of end-stage apoptosis. Using in vitro-stimulated effectors specific for the ovalbumin K(b)OVA(257) (OT-I) and influenza A virus D(b)NP(366) and D(b)PA(224) epitopes, no significant correlation was found between the duration of CTL contact and the time to phosphatidylserine exposure or loss of membrane integrity. Furthermore, there were minimal indications that transgenic T cells specific for the K(b)OVA(257) epitope (TCR) diversity had any effect. However, when the analysis was repeated with D(b)NP(366) and D(b)PA(224)-specific CTLs recovered directly from the lungs of mice with influenza pneumonia, the lower avidity D(b)NP(366)-specific set was found to elute much more quickly. Shorter contact time may allow individual CTLs to lyse more targets, suggesting that lower TCR/epitope avidity may be more beneficial than higher epitope avidity for cell-mediated immunity.

References

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Citations

May 2, 2012·Proceedings of the National Academy of Sciences of the United States of America·Nicholas Stephen Rennie SandersonPedro R Lowenstein
Feb 22, 2011·Immunology Letters·Bettina WeigelinPeter Friedl
Mar 17, 2010·Current Opinion in Immunology·Misty R Jenkins, Gillian M Griffiths
Jun 16, 2009·Current Opinion in Immunology·Stephen J TurnerPeter C Doherty
Jun 26, 2012·Trends in Cell Biology·Ken R Duffy, Philip D Hodgkin
Nov 22, 2016·Nature Communications·Michal Bassani-SternbergAngela M Krackhardt
Nov 1, 2013·Nature Communications·Sophie A ValkenburgKatherine Kedzierska
Dec 2, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jin-Shu HeHanne L Ostergaard

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