We next analyzed the sequence diversity in the frequently targeted epitopes compared to those that were restricted by the same HLA class I allele but rarely targeted, since we had demonstrated previously for selected HIV-1-specific CD8+ T cell epitopes that their sequence heterogeneity in the circulating HIV-1 strains can be an important determinant for the ability of the immune system to recognize these epitopes [24,32–35], whereas some epitopes are only targeted later in infection despite the presence of the original wild-type sequence in the initial infecting viral strain [21]. The gene discussed is CD8A; the disease is infection.