The sequences of a set of 63 peptides of demonstrated T immunogenicity have been analyzed and compared with two different randomly generated sets of sequences. This study indicates a statistically significant tendency of T immunogenic peptides to be constituted of clusters of rare tetrapeptides, as evaluated from the available sequence data banks. This result has been used to locate potential T epitopes in the human immunodeficiency virus (HIV) gag protein. Four peptides corresponding to the best candidate T epitopes (chosen in regions of conserved sequence among different virus isolates) have been synthesized and found to be recognized by a HIV-1-specific, HLA-A2-restricted human cytotoxic T cell line.