HLA B*5701-positive long-term nonprogressors/elite controllers are not distinguished from progressors by the clonal composition of HIV-specific CD8+ T cells

Abstract

To better understand the qualitative features of effective human immunodeficiency virus (HIV)-specific immunity, we examined the TCR clonal composition of CD8(+) T cells recognizing conserved HIV p24-derived epitopes in HLA-B*5701-positive long-term nonprogressors/elite controllers (LTNP/EC) and HLA-matched progressors. Both groups displayed oligoclonal HLA-B5701-restricted p24-specific CD8(+) T-cell responses with similar levels of diversity and few public clonotypes. Thus, HIV-specific CD8(+) T-cell responses in LTNP/EC are not differentiated from those of progressors on the basis of clonal diversity or TCR sharing.

Fig 1

Clonal composition of HLA-B5701/HIV Gag p24 tetramer-positive CD8⁺ T-cell populations in LTNP/EC and progressors. (A and B) Summary data showing the frequencies of each TCR clonotype (Table 2) relative to the frequencies of the corresponding HLA B5701/HIV Gag p24 tetramer-positive CD8⁺ T cells in 7 HLA-B*5701-positive LTNP/EC (A) and 8 HLA-B*5701-positive progressors (B). Three HLA-B5701/HIV Gag p24 tetramers containing B57 bound to one of three immunodominant Gag p24-derived epitopes (I, IW9; K, KF11; and Q, QW9) were used to stain and sort antigen-specific CD8⁺ T cells for clonotypic analysis. Results for two different specificities are shown for patients 4, 8, 34, 107, and 131. The numbers above each stacked bar denote the total number of clonotypes for the depicted epitope-specific CD8⁺ T-cell population.

Fig 2

Comparison of HLA-B5701/HIV Gag p24 tetramer-positive CD8⁺ T-cell repertoire diversities between HLA-B5701-positive LTNP/EC and progressors (A to D). Two diversity measures, the standardized number of clonotypes (A and B) and Simpson's diversity index (C and D), were estimated for a standard sample size of 29 TCRβ sequences per repertoire. Simpson's diversity index accounts for both the variety of amino acid sequence clonotypes and their clone sizes, ranging in value from 0 (minimal diversity) to 1 (maximal diversity). Horizontal lines indicate the median values. Squares, circles, and triangles represent the HLA-B5701-restricted HIV Gag p24-derived epitopes IW9, KF11, and QW9, respectively.