Lack of strong immune selection pressure by the immunodominant, HLA-A*0201-restricted cytotoxic T lymphocyte response in chronic human immunodeficiency virus-1 infection.

Abstract

Despite detailed analysis of the HIV-1-specific cytotoxic T lymphocyte response by various groups, its relation to viral load and viral sequence variation remains controversial. We

A Novel Approach to the Analysis of Specificity, Clonality, and Frequency of HIV-Specific T Cell Responses Reveals a Potential Mechanism for Control of Viral Escape

“…This epitope has been shown to resist escape from CD8 ϩ T cells, partially because CD8 ϩ T cells can recognize multiple variants of this epitope (26,27). Six different TCR clonotypes targeted this epitope in subject TX7.…”

“…Then during therapy, three variants emerged, SLYNTVAVL, SLYNTIATL, and SLYN-TIAVL, the latter being predominant. None of the amino acid changes were at MHC anchor residues, and all four peptides can bind to HLA-A2, but have markedly variable recognition by different T cell clones (27). Later, the original sequence reemerged and persisted.…”

Discovery and characterization of highly immunogenic and broadly recognized mimics of the HIV‐1 CTL epitope Gag77–85

“…About 70% of chronically HIV-infected, HLA-A2-positive individuals have circulating CTL that recognize the Gag p17-derived epitope SLYNTVATL (SL9) [8,9]. Although the in vivo effectiveness of SL9-specific CTL has been questioned [8][9][10][11][12], there may at least be a partial benefit from these responses.…”

“…Although the in vivo effectiveness of SL9-specific CTL has been questioned [8][9][10][11][12], there may at least be a partial benefit from these responses. Interestingly, although HLA-A*0201-restricted SL9 responses are often dominant in chronic infection, they are rarely induced during acute HIV infection [11,13].…”

“…Interestingly, although HLA-A*0201-restricted SL9 responses are often dominant in chronic infection, they are rarely induced during acute HIV infection [11,13]. The intermediate binding affinity of SL9 to HLA-A*0201 [9] may contribute to its subdominance at an early stage of the infection. Alternatively, SL9 has been described as a help-independent epitope that would arise late in infection when CD4 counts are reduced and IL-2-induced cell death would be diminished [14].…”