Tumor-infiltrating CD8 + T cells are associated with improved survival of patients with Merkel cell carcinoma (MCC), an aggressive skin cancer causally linked to Merkel cell polyomavirus (MCPyV). However, CD8 + T-cell infiltration is robust in only 4%-18% of MCC tumors. We characterized the T-cell receptor (TCR) repertoire restricted to one prominent epitope of MCPyV (KLLEIAPNC, "KLL") and assessed whether TCR diversity, tumor infiltration, or T-cell avidity correlated with clinical outcome. HLA-A*02:01/KLL tetramer + CD8 + T cells from MCC patient peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TIL) were isolated via flow cytometry. TCRβ (TRB) sequencing was performed on tetramer + cells from PBMC or TIL (n = 14) and matched tumors (n = 12). Functional avidity of T-cell clones was determined by IFNγ production. We identified KLL tetramer + T cells in 14% of PBMC and 21% of TIL from MCC patients. TRB repertoires were diverse (mean of 12 and 29 clonotypes/patient in PBMC and TIL, respectively) and mostly private. An increased fraction of KLL-specific TIL (> 1.9%) was associated with significantly increased MCC-specific survival P = 0.0009). Forty-two