We analyzed public data on CTL sensitivity and created a visualization of how CTLs react to single amino acid substitutions. Lee et al. [10] analyzed the specificity of CTL responses against the immunodominant HLA-A2 restricted HIV Gag epitope SLFNTVATL (SFL9). IFNc production was measured in response against all 171 single mutant variants of SFL9. Abrogated TCR responses were mostly due to loss of TCR binding as the majority of SFL9 variants retained binding to MHC. The cross reactivity data for the three data sets: G10, T4 and PBMC were converted into a position-specific-scoring-matrix (PSSM) as described in Materials and Methods. The recognition motif of the T4 clone (the PSSM matrix) is visualized in Fig. 1A as a Logo plot [11] . The plot shows a stack of the possible amino acid mutations on each position in SLFNTVATL (x-axis). The height of the stack is reciprocal to the number of tolerated mutations (i.e., it indicates the degree of T cell recognition specificity at this position, see Materials and Methods). Few tolerated mutations translate into tall stacks while many tolerated mutations show up as short stacks (bars). For example, in position five, only one variant is tolerated (T5S) and is shown as a tall bar. The remaining variants on position 5 were unable to bind the TCR even though the binding to MHC was mostly preserved. On the contrary, in position one, 18 out of 19 variants preserved the TCR recognition. The logo plot for CTL clone T4 given in Fig. 1A suggests that the central peptide positions are most important for peptide-TCR binding, which is in agreement with earlier data [12, 13] . The average Shannon information [14] plot for T4, G10 clones and PBMC is shown in Fig. 1C . This figure also indicates that positions 2-6 and 8-9 are most important for peptide recognition whereas position one is consistently of little importance. Position 2 and 9 are the main positions determining peptide binding to the HLA-A*0201 molecule, see Fig. 1B . Thus, positions 3-6 and 8 were consistently involved in the primary TCR recognition motif. Moreover, the sequence motif for T4 clone suggests that tolerated substitutions tend to be conservative with respect to the original epitope sequence, SLFNTVATL. Examples are F3Y (both non-polar and aromatic), T5S (both polar), and V6I (both aliphatic). Similar observations on tolerated substitutions were made for the other two CTL clones (data not shown). Taken together, these data suggest that amino acid similarity could be a major component of T cell recognition.