1. The Negative Checkpoint Receptor TIGIT Marks Exhausted T cells During SIV Infection and Correlates with SIV Disease Progression Gabriela Webb Vaccine and Gene Therapy Institute Oregon Health and Science University July 21, 2015

2. CD8+ T cell TIGIT CD155 PD1 PDL1 Proliferation Cytokine production TCR + - - Rhesus TIGIT shares 88.1% sequence homology with human TIGIT High antigenic load environment  T cell exhaustion

3. TIGIT expression is increased in SIV+ RMs and correlates with viral load

4. TIGIT is also found on SIV-specific CD8+ T cells in RMs with full cART suppression of SIV viremia SIV-specific CD8+ T cells co-express TIGIT & PD-1

5. TIGIT+ CD8+ T cells produce less IFNγ when stimulated Single and dual blockade of PDL1 and TIGIT restores CD8+ T cell proliferation Summary TIGIT is expressed on SIV-specific CD8+ T cells and proliferative capacity can be restored with single or dual blockade Rhesus TIGIT in SIV infection recapitulates what is observed with human TIGIT in HIV infection  Glen Chew (TUAA02 Rm 211-214) TIGIT/PD1 blockade could be used in conjunction with “shock and kill” approaches

6. Acknowledgements Oregon Health & Science University Jonah Sacha Benjamin Burwitz Shaheed Abdulhaqq Helen Wu Jason Reed Katherine Hammond Reesab Pathak Scott Hansen University of Hawaii Lishomwa Ndhlovu Glen Chew – TUAA02 Tsuyoshi Fujita Bristol-Myers Squibb Alan Korman Mark Maurer