Cohort characteristics.

<p>Cohort characteristics.</p

Immunodominant CMV-specific CD8+ T-cell responses within pp65, IE-1 and IE-2 measured by IFN-g ELISpot assay for CMV+ subjects.

<p>(A) Percentage responders to each protein-covering peptide pool. (B) Percentage responders among 152 CMV+ individuals to pp65 15mer overlapping peptides that were targeted by >4% of the study population. (C) Percentage responders among 95 CMV+ individuals to IE-1 15mer overlapping peptides that were targeted by >3% of the study population. (D) Percentage responders among 92 CMV+ individuals to IE-2 15mer overlapping peptides that were targeted by >3% of the study population.</p

Cohort characteristics.

<p>Cohort characteristics.</p

HLA associations with the remaining 15-mer OLP’s in CMV pp65, IE-1 and IE-2 that were targeted by ≥4% of the study cohort.

<p>HLA associations with the remaining 15-mer OLP’s in CMV pp65, IE-1 and IE-2 that were targeted by ≥4% of the study cohort.</p

Individuals making CD8+ T cell responses against CMV IE-2 epitope HLA-B*44:03-NW8.

<p>(A) Representative FACS plot of a Durban cohort subject 202-30-0064 (expressing HLA-B*44:03/B*58:01) to HLA-B*44:03-restricted NW8 tetramer. (B) FACS plot of subject R048 (HLA-A*29:02, -A*6802, -B*15:03, -B*44:03, -C*02:10, -C07:01) with NW8 tetramer and HLA-mismatched tetramer. (C) FACS plot of a TVC subject R112 (HLA-A*23:01, -A*3002, -B*18:01, -B*18:01, -C*02:02, -C07:04) to HLA-B*44:03-restricted NW8 tetramer, as B*44:03-negative control. The FACS plots show tetramer-specific cells expressed as the percentage of live CD3+ CD8+ T-cells. (D) Percentage of live CD3+ CD8+ tetramer-specific T-cells in individuals expressing HLA-B*44:03 measured using the B*44:03-NW8 tetramer.</p

Validation of novel CD8+ T-cell epitopes in CMV using HLA-Class I tetramers.

<p>(A) Flow cytometry plot of CD8+ T-cell responses from a Durban cohort subject SK-251 (HLA-A*02:05, -A*30:01, -B*42:01, -B*58:01, -C*07:01, -C*017:01) to HLA-A*30:01-restricted IE-2-342/343 epitope-KK9 and an HLA-mismatched tetramer stain as a control. (B) Flow cytometry plot from a Durban cohort subject SK-331 (HLA-A*30:01, -A*66:01, -B*42:01, -B*58:02, -C*06:02, -C*017:01) to B*42:01-restricted pp65-66/67 epitope RL11 and an HLA-mismatched tetramer stain as a control. The plots show gated live CD3+ T-cells; the number shown above each gate is the percentage of live CD3+ CD8+ cells that are tetramer-specific.</p

Phenotypic frequencies of closely related HLA I molecules and their impact on CMV specific CD8+ T-cell hierarchies.

<p>(A) The phenotypic frequency of some of the HLA class I molecules in A2 superfamily in white populations [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189612#pone.0189612.ref028" target="_blank">28</a>] and our African cohort. (B) The percentage of subjects with HLA alleles A*02:01 (n = 23), A*02:02 (n = 10) and A*02:05 (n = 16), responding to epitope (NLVPMVATV) in pp65-123/124 peptide and predicted epitope (FVFPTKDV) in pp65-46/47 peptide. (C) The phenotypic frequency of the HLA class I molecules in B07 superfamily in white populations [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0189612#pone.0189612.ref028" target="_blank">28</a>] and our African cohort. (D) The percentage of subjects with B*07:02 (n = 21), B*35:01 (n = 10), B*39:10 (n = 6), B*42:01 (n = 26) and B*81:01(n = 12) alleles in our African cohort responding to predicted epitopes in pp65, GPISGHVL (OLP-4), RPHERNGFTVL (OLP-66/67) and TPRVTGGGAM (OLP-104/105). The percentage of subjects in our African cohort responding to predicted epitope in IE-1, TMYGGISLL (OLP-212/213) with HLA-B*07:02 (n = 11), B*35:01 (n = 6) B*39:10 (n = 5), B*42:01 (n = 19) and B*81:01(n = 1) alleles.</p

HLA associations with the most targeted 15-mer OLP’s in CMV pp65, IE-1 and IE-2.

<p>HLA associations with the most targeted 15-mer OLP’s in CMV pp65, IE-1 and IE-2.</p

Indications for ART Initiation in 222 children whose CD4 counts were above CD4 treatment thresholds.

<p>^a Not within the guidelines for ART initiation in children</p><p>Indications for ART Initiation in 222 children whose CD4 counts were above CD4 treatment thresholds.</p

Sex differences in CD4+ T cell count, CD4% and viral load, amongst 2,101 ART-naïve South African children.

<p>A. Absolute CD4 counts changes with age. B. CD4% changes with age. C. Viral load changes with age. In each panel, the solid lines are Loess-smoothed regression lines for female children and the dotted lines are Loess-smoothed regression lines for male children. A multivariable linear regression model, with both sex and age as covariates, shows significantly lower absolute CD4 counts in males (p = 0.005); significantly lower CD4% in males (p = 3.7x10^-7); and no significant difference in viral load between the sexes.</p