Major alleles expressed as determined by MHC I genotyping.

<p>Major alleles expressed as determined by MHC I genotyping.</p

Increased anentropic specificity of SIV-specific CD8 T cell responses between weeks 5 and 20 after SIVΔnef vaccination.

<p>The response conservation index, a measure of the CD8 T cell response weighted negatively for entropy, increases for every animal between weeks 5 and 20 (p = 0.0156). The response conservation index for an animal at a given time point is calculated as<math><mrow><mo>∑</mo><mrow><mi>i</mi><mo>=</mo><mn>0</mn></mrow><mi>n</mi><mrow><msub><mi>F</mi><mi>i</mi></msub></mrow><mo stretchy="false">(</mo><mn>1</mn><mo>−</mo><msub><mi>E</mi><mi>i</mi></msub><mo stretchy="false">)</mo></mrow></math>, where F is the frequency of each epitope-specific CD8 T cell response as a fraction of the total magnitude of the response, E is the entropy of the epitope, and n is the number of epitope-specific CD8 T cell responses.</p

Epitope mapping reveals a change in the CD8 T cell repertoire and in immunodominance.

<p>(A) Of the 37 CD8 T cell epitopes mapped for 6 SIVΔnef-vaccinated animals at week 5, only 14 epitopes were recognized at week 20. Approximately two thirds of the epitopes recognized at week 20 were novel responses not previously detected. (B) The entropy of the immunodominant epitope decreased significantly between weeks 5 and 20 (p = .039).</p

Sequence evolution and CD8 T cell responses overlap, positionally and temporally.

<p>(A) In animal 225–97, 7 of the 9 highest frequency nonsynonymous mutations at week 20 were within mapped CD8 T cell epitopes. (B) Epitope-specific CD8 T cell responses declined as their epitopes escaped. Time of 50% escape is shown between parentheses. (C) The sequence evolution of 4 CD8 T cell epitopes mapped from animal 225–97 demonstrates the dynamic nature of viral escape. In all cases, escape variants were over taken by other variants at a later time point.</p

Increased CD8 T cell repertoire depth during SIVΔnef vaccination.

<p>(A) FW9, an epitope mapped in animal 256–00, escaped the CD8 T cell response by mutating a histidine into a tyrosine (H831Y). The escape mutant was recognized at week 38 but not at week 5, when the original epitope was mapped. (B) The GY9 epitope was recognized at week 5 in animal 256–00 as well as week 38, while its escape variant K76R was recognized only at week 38. The third escape variant S77G was not recognized at either time point.</p

Escaped responses contribute to the cumulative breadth of the CD8 T cell repertoire.

<p>(A) No change in breadth of the CD8 T cell response was observed as measured by the number epitope-specific CD8 T cell responses per animal at weeks 5 and 20. (B) The cumulative breadth at week 20 was significantly higher than the breadth at Week 5 (p = 0.0036). The cumulative breadth at week 20 included all the week 5 epitope responses, even if they were not detected at week 20. (C) Phenotypic analysis of SL8 tetramer+ CD8 T cells from peripheral blood. SL8-specific CD8 T cells exhibited a central memory profile at week 20, as demonstrated by increased expression of CD28 (p = 0.0087), CCR7 (p = 0.0006) and CD127 (p<0.0001) markers and a decrease in perforin (p<0.0001) and Ki67 (p = 0.0194). (D) Tat SL8 epitope heat maps showing 82% and 94% percent variation at week 4 for animals 201–02 and 206–00, respectively. Below, two graphs show the primary and recall SL8-specific CD8 T cell responses (squares) as measured by Mamu-A*01-SL8 tetramer staining (left) and IFN-γ ELISPOT (right) in the context of plasma viral loads of SIVΔnef (triangles) and SIVmac251 challenge virus (circles) in 201–02 (dark blue) and 206–00 (green).</p

Evolution of the epitope specificity of SIV-specific CD8 T cell responses in SIVΔnef-vaccinated animals.

<p>(A) The total magnitude of the PBMC CD8 T cell response as measured by IFN-γ ELISPOT assays using whole protein overlapping peptide pools. (B) The breadth of the PBMC CD8 T cell response as measured by the average number of positive pools at weeks 5 and 20. (C) The magnitude and the breadth of lymph node CD8 T cell responses. The total magnitude of lymph node CD8 T cell response to SIV was determined by adding the responses for all 30 peptide pools spanning the entire SIVΔnef proteome. (D) The Gag and Pol-specific CD8 T cell response as a fraction of the total SIV-specific CD8 T cell response increased significantly between weeks 5 and 16/20 (p<0.0001), plateauing at week 16.</p

An application of HOMER and ACMANT for homogenising monthly precipitation records in Ireland.

Climate change studies based only on raw long-term data are potentially flawed due to the many breaks introduced from non-climatic sources, consequently quality controlled and homogenised climate data is desirable for basing climate related decision making on. Seasonal cycles of precipitation in Ireland and the UK are projected to become more marked as the climate changes, and regional extremes in summer dry spells and winter precipitation have been recorded in recent years. Therefore to analyse and monitor the evolution of precipitation patterns across Ireland, quality controlled and homogenous climate series are needed

Principal component analysis of transcription factor expression profiles from SIV-specific MHC tetramer-sorted CD8⁺ T cells and sorted CD8⁺ T cell subsets.

<p>(<b>A</b>) Plot of principal components 1 vs. 2, and 2 vs. 3 for each of the expression profiles assessed in sorted naïve and memory CD8⁺ T cell subsets isolated from healthy control animals (n = 5), and SIV-specific MHC tetramer-sorted CD8⁺ T cells isolated from animals (n = 4) at week 5 or week 20 following SIVΔnef vaccination. Principal components 1, 2 and 3 explain 92% of cumulative total variance. (<b>B</b>) PCA loading factors for each transcription factor.</p