YV9 pentamer
description
Transcript of YV9 pentamer
Washington D.C., USA, 22-27 July 2012www.aids2012.org
Enhanced TCR Affinity Imparts Specificity to Reverse Transcriptase Inhibitor Resistance-
Associated Mutations
TCR Kd t ½ (sec)
YV9 wt 6.72μM 2.69359 5.06μM 5.28361 1.31μM 9.56383 .86μM 14.43384 .29μM 27.75
UNT YV9 359 361 383 384
YV9 pentamer
TCR α TCR β
Washington D.C., USA, 22-27 July 2012www.aids2012.org
High affinity YV9 Pol TCRs recognize and respond to drug escape mutations
(Efavirenz)
(Nevirapine) (Lamivudine)
IL-2
TNFα
Washington D.C., USA, 22-27 July 2012www.aids2012.org
High Affinity YV9 TCR can endow CD4 with effector function
• MHC Class I restricted haTCR Transduction of CD4 cells imparts effector-like function
• Enhanced affinity increases breadth and sensitivity of epitope recognition to include common drug escape mutations
• High affinity YV9 TCRs may be attractive as a potential immunotherapy agent to be used in combination with current ART chemotherapeutics
IL-2
45.7% transduced
70.8% transduced
77.2% transduced
TNFα
CONCLUSIONSKT.A2.CD64.YV9
Acknowledgements: A.Klattenhoff, C. Baiduc, J.L. Riley