Cytotoxic T lymphocytes (CTLs) play a vital part in controlling viral replication during human
viral infections. Most studies in human
infections have focused on CTL specificities in
chronic infection and few data exist regarding the specificity of the initial CTL response induced in acute
infection. In this study, HIV-1
infection in persons expressing human histocompatibility leukocyte
antigen (
HLA)-A*0201 was used as a means of addressing this issue. In
chronic infection, the dominant
HLA-A*0201-restricted CTL response is directed towards the
epitope SLYNTVATL ("SL9") in p17 Gag (residues 77-85). This
epitope is targeted by 75% of
HLA-A*0201-positive adults, and the magnitude of this A*0201-SL9 response shows a strong negative association with viral load in progressive
infection. Despite using the highly sensitive
peptide-major histocompatibility complex tetramer and intracellular
cytokine assays, responses to the SL9
epitope were not detectable in any of 11
HLA-A*0201-positive subjects with acute HIV-1
infection (
P = 2 x 10(-6)), even when assays were repeated using the SL9
peptide variant that was encoded by their autologous virus. In contrast, multiple responses (median 3) to other
epitopes were evident in 7 of the 11 A*0201-positive subjects. Longitudinal study of two subjects confirmed that the A*0201-SL9 response emerged later than other CTL responses, and after viral set point had been reached. Together, these data show that the CTL responses that are present and that even may dominate in
chronic infection may differ substantially from those that constitute the initial
antiviral CTL response. This finding is an important consideration in
vaccine design and in the evaluation of
vaccine candidates.