Substantial Differences in Specificity of HIV-Specific Cytotoxic T Cells in Acute and Chronic HIV Infection

Abstract

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 × 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.

Cellular immune responses against hepatitis C virus: the evidence base 2002

“…As an example, a single 'clearer' who made 8 separate CTL responses made only one to a previously mapped epitope (restricted by HLA-A2), and even this was not the dominant HLA-A2 restricted response [10], and similar findings are obtained in studies of those persistently infected [21]. This is similar to the situation in HIV where an epitope in p17 gag (SLYNTVATL) has been found to be frequently targeted in HLA-A2 positive individuals, but during acute disease, it is rarely seen -other epitopes are likely to be much more important at this critical stage [22].…”

Comprehensive analyses of CD8+ T cell responses during longitudinal study of acute human hepatitis C

“…Despite recognition of a combined 51 antigens and ongoing viremia with sequence evolution, no antigens were first recognized more than 6 months after infection in any subject. In contrast, new responses to HIV-1 and HTLV-1 have been detected after the first 6 months of infection, 43,44 suggesting that HCV may interfere with this process in some way.…”

Dominance of Virus-Specific CD8 T Cells in Human Primary Cytomegalovirus Infection

“…After a median time of approximately 30 d off therapy (29,29, and 47 d, respectively), the patients reported to the hospital with mild CMV-related symptoms such as fever and myalgia. All patients showed detectable CMV-DNA that was accompanied by the induction of both CMV-specific T cell and antibody responses.…”