(A) Heatmap of the binding score for different dextramers of different TCRs using the same CASSIRSSYEQYF βCDR3, in two donors. The recognition properties are remarkably similar whatever the βCDR3. The polyspecificity is oriented toward the recognition of common viruses such as influenza, EBV, and CMV. (B) We identified another βCDR3 from donor 1 that is associated with a strong binding to one A1101 dextramer presenting an EBV peptide, when associated to many different αCDR3. The binding to the other A03 and A011 dextramers is weaker and seems to depend more on the αCDR3. The same βCDR3was also found in a second donor, associated with different αCDR3s. In this donor, the binding appeared αCDR3 dependent, even for the stronger binding to the A1101 dextramer presenting an EBV peptide. Altogether, these identify different binding patterns than in (A). (C) We identified a βCDR3 from donor 3 that binds preferentially to A*03 and A*11 dextramers. However, it binds to only four out of five of these. Moreover, we identified this same βCDR3 in two other cells from donors 1 and 4, but that was associated with different αCDR3s. Except for only one weak binding, these TCRs do not show binding to the A*03 and A*11 dextramers, identifying a different binding pattern than in (A). Altogether, (A), (B), and (C) reveal that the binding patterns of the A*03 and A*11 dextramers are TCR dependent and cannot be due to their interaction with other molecules that interact with MHCs sur as KIRs. MHC, major histocompatibility complex; TCR, T-cell receptor.