Oligoclonal expansions of CD8(+) T cells in chronic HIV infection are antigen specific

Abstract

Acute HIV infection is associated with a vigorous immune response characterized by the proliferation of selected T cell receptor V beta (BV)-expressing CD8(+) T cells. These 'expansions', which are commonly detected in the peripheral blood, can persist during chronic HIV infection and may result in the dominance of particular clones. Such clonal populations are most consistent with antigen-driven expansions of CD8(+) T cells. However, due to the difficulties in studying antigen-specific T cells in vivo, it has been hard to prove that oligoclonal BV expansions are actually HIV specific. The use of tetrameric major histocompatibility complex-peptide complexes has recently enabled direct visualization of antigen-specific T cells ex vivo but has not provided information on their clonal composition. We have now made use of these tetrameric complexes in conjunction with anti-BV chain-specific monoclonal antibodies and analysis of cytotoxic T lymphocyte lines/clones to show that chronically clonally expanded CD8(+) T cells are HIV specific in vivo.

Figure 1

The TCR usage of HIV-specific CD8⁺ T cells in vivo. PBL taken from patients 868 and 003 were stained with HLA A2–SLYNTVATL tetrameric complexes. The PBL of patient 868 was also stained with a HLA B27–KRWIIMGLNK tetrameric complex, whereas the PBL taken from patient 065 was stained with the HLA A2–ILKEPVHGV tetramer. The tetramer was used to stain PBL in conjunction with CD8 and a panel of BV chain–specific mAbs. In patient 868, the A2-Gag tetramer stained 1.74% of the circulating CD8⁺ T cells, of which BV5S2 made up 75% (A). The B27-Gag tetramer also stained 4.32% of the circulating CD8⁺ T cells from this patient, of which BV13S1 and BV5S2 made up 37 and 22%, respectively (B). In patient 065, the A2-Pol tetramer stained 1.14% of the circulating CD8⁺ T cells, of which BV3 made up 100% (C).

Figure 1

The TCR usage of HIV-specific CD8⁺ T cells in vivo. PBL taken from patients 868 and 003 were stained with HLA A2–SLYNTVATL tetrameric complexes. The PBL of patient 868 was also stained with a HLA B27–KRWIIMGLNK tetrameric complex, whereas the PBL taken from patient 065 was stained with the HLA A2–ILKEPVHGV tetramer. The tetramer was used to stain PBL in conjunction with CD8 and a panel of BV chain–specific mAbs. In patient 868, the A2-Gag tetramer stained 1.74% of the circulating CD8⁺ T cells, of which BV5S2 made up 75% (A). The B27-Gag tetramer also stained 4.32% of the circulating CD8⁺ T cells from this patient, of which BV13S1 and BV5S2 made up 37 and 22%, respectively (B). In patient 065, the A2-Pol tetramer stained 1.14% of the circulating CD8⁺ T cells, of which BV3 made up 100% (C).

Figure 1

The TCR usage of HIV-specific CD8⁺ T cells in vivo. PBL taken from patients 868 and 003 were stained with HLA A2–SLYNTVATL tetrameric complexes. The PBL of patient 868 was also stained with a HLA B27–KRWIIMGLNK tetrameric complex, whereas the PBL taken from patient 065 was stained with the HLA A2–ILKEPVHGV tetramer. The tetramer was used to stain PBL in conjunction with CD8 and a panel of BV chain–specific mAbs. In patient 868, the A2-Gag tetramer stained 1.74% of the circulating CD8⁺ T cells, of which BV5S2 made up 75% (A). The B27-Gag tetramer also stained 4.32% of the circulating CD8⁺ T cells from this patient, of which BV13S1 and BV5S2 made up 37 and 22%, respectively (B). In patient 065, the A2-Pol tetramer stained 1.14% of the circulating CD8⁺ T cells, of which BV3 made up 100% (C).