Because negative selection of immature thymocytes remove high affinity TCR specific for self-antigens [7] , we expected that this should leave a ''hole'' in the T cell repertoire around negative selecting self-antigens. Hence, if an infected cell presents a nonself antigen that is highly similar to a negative selecting self-antigen, then this foreign antigen might not be matched by any available TCR which could provide an explanation for why around half of foreign pMHC do not generate a T cell response [3, 4, 21] . We tested this hypothesis for HLA-A2 restricted HIV-1 response and showed that the absence of T cell response to part of the non-confirmed (i.e. putative non-immunogenic) HLA-A2 restricted HIV-1 peptides can be explained by their similarity to self antigens. These results are in agreement with a recent study by Rolland et al. [24] , who showed a trend of more-selflikeness (measured in terms of number of shared amino acids) among HIV peptides with no detectable CTL responses in a large study group. We predict that the correlation found by Rolland et al. would be stronger if amino acid similarity is taken into account.