YV9 pentamer

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Washington D.C., USA, 22-27 July 2012 www.aids2012.org Enhanced TCR Affinity Imparts Specificity to Reverse Transcriptase Inhibitor Resistance-Associated Mutations TCR Kd t ½ (sec) YV9 wt 6.72μM 2.69 359 5.06μM 5.28 361 1.31μM 9.56 383 .86μM 14.43 384 .29μM 27.75 UNT YV9 359 361 383 384 YV9 pentamer TCR α TCR β

description

Enhanced TCR Affinity Imparts Specificity to Reverse Transcriptase Inhibitor Resistance-Associated Mutations. YV9 pentamer. TCR α. TCR β. High affinity YV9 Pol TCRs recognize and respond to drug escape mutations. ( Efavirenz ). IL-2. TNF α. ( Nevirapine ). (Lamivudine). - PowerPoint PPT Presentation

Transcript of YV9 pentamer

Page 1: 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

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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

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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