Since improved TCR affinity (KD ≤ 1 μM) mainly resulted from increased contacts with the HLA-A2 (referred to as A2) backbone [17], we hypothesized that A2-(self) molecules per se may directly trigger chronic interactions with affinity-increased TCRs and modulate the functional state of tumor-redirected CD8 T cells, even in the absence of cognate peptide. Here, CD8A is linked to neoplasm.