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The efficiency of the human CD8+ T cell response: how should we quantify it, what determines it, and does it matter?

Elemans M, Seich Al Basatena NK, Asquith B - PLoS Comput. Biol. (2012)

Bottom Line: Multidisciplinary techniques, in particular the combination of theoretical and experimental immunology, can address questions about human immunity that cannot be answered by other means.From the turnover of virus-infected cells in vivo, to rates of thymic production and HLA class I epitope prediction, theoretical techniques provide a unique insight to supplement experimental approaches.Here we present our opinion, with examples, of some of the ways in which mathematics has contributed in our field of interest: the efficiency of the human CD8+ T cell response to persistent viruses.

View Article: PubMed Central - PubMed

Affiliation: Section of Immunology, Imperial College School of Medicine, London, United Kingdom.

ABSTRACT
Multidisciplinary techniques, in particular the combination of theoretical and experimental immunology, can address questions about human immunity that cannot be answered by other means. From the turnover of virus-infected cells in vivo, to rates of thymic production and HLA class I epitope prediction, theoretical techniques provide a unique insight to supplement experimental approaches. Here we present our opinion, with examples, of some of the ways in which mathematics has contributed in our field of interest: the efficiency of the human CD8+ T cell response to persistent viruses.

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Related in: MedlinePlus

The variation in outcome that can be explained by individual HLA class I alleles in HIV-1, HTLV-1 and HCV infections.The explained fraction (EF) was calculated following Nelson [82]; data for HCV and HTLV-1 were taken from [56], and data for HIV-1 were taken from [40], [83]. 95% confidence intervals were estimated by bootstrapping the data 5,000 times, trimming the 5% extremes, and then calculating the range in which 95% of the remaining data lay. Due to linkage between the HLA alleles, the EF is not additive; so for instance, in HTLV-1 infection, the three alleles HLA-A*02, C*08, and B*54 together only explain 6.6% of the outcome. The outcomes explained are HCV: spontaneous clearance v persistence; HTLV-1: asymptomatic carriage v HAM/TSP; HIV-1: elite control v viremic control v progression.
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pcbi-1002381-g003: The variation in outcome that can be explained by individual HLA class I alleles in HIV-1, HTLV-1 and HCV infections.The explained fraction (EF) was calculated following Nelson [82]; data for HCV and HTLV-1 were taken from [56], and data for HIV-1 were taken from [40], [83]. 95% confidence intervals were estimated by bootstrapping the data 5,000 times, trimming the 5% extremes, and then calculating the range in which 95% of the remaining data lay. Due to linkage between the HLA alleles, the EF is not additive; so for instance, in HTLV-1 infection, the three alleles HLA-A*02, C*08, and B*54 together only explain 6.6% of the outcome. The outcomes explained are HCV: spontaneous clearance v persistence; HTLV-1: asymptomatic carriage v HAM/TSP; HIV-1: elite control v viremic control v progression.

Mentions: HLA Associations. Surprisingly, although associations between particular HLA class I molecules and clinical outcome are highly significant, the fraction of variation in outcome that can be explained by HLA alleles is rather small (Figure 3), though this does increase by a factor of 2–4 in KIR2DL2+ individuals. Clearly, HLA associations tell us about differences in HLA molecules, so a small explained fraction does not necessarily mean CD8+ T cell responses are unimportant; it could be that all CD8+ T cell responses are rather similar regardless of their restriction. However, it does caution us that we should not assume that the CD8+ T cell response is important just because HLA associations are highly significant. Furthermore, it implies that the majority of between-individual variation in clinical outcome is unlikely to be due to differences in HLA class I genotype.


The efficiency of the human CD8+ T cell response: how should we quantify it, what determines it, and does it matter?

Elemans M, Seich Al Basatena NK, Asquith B - PLoS Comput. Biol. (2012)

The variation in outcome that can be explained by individual HLA class I alleles in HIV-1, HTLV-1 and HCV infections.The explained fraction (EF) was calculated following Nelson [82]; data for HCV and HTLV-1 were taken from [56], and data for HIV-1 were taken from [40], [83]. 95% confidence intervals were estimated by bootstrapping the data 5,000 times, trimming the 5% extremes, and then calculating the range in which 95% of the remaining data lay. Due to linkage between the HLA alleles, the EF is not additive; so for instance, in HTLV-1 infection, the three alleles HLA-A*02, C*08, and B*54 together only explain 6.6% of the outcome. The outcomes explained are HCV: spontaneous clearance v persistence; HTLV-1: asymptomatic carriage v HAM/TSP; HIV-1: elite control v viremic control v progression.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3285570&req=5

pcbi-1002381-g003: The variation in outcome that can be explained by individual HLA class I alleles in HIV-1, HTLV-1 and HCV infections.The explained fraction (EF) was calculated following Nelson [82]; data for HCV and HTLV-1 were taken from [56], and data for HIV-1 were taken from [40], [83]. 95% confidence intervals were estimated by bootstrapping the data 5,000 times, trimming the 5% extremes, and then calculating the range in which 95% of the remaining data lay. Due to linkage between the HLA alleles, the EF is not additive; so for instance, in HTLV-1 infection, the three alleles HLA-A*02, C*08, and B*54 together only explain 6.6% of the outcome. The outcomes explained are HCV: spontaneous clearance v persistence; HTLV-1: asymptomatic carriage v HAM/TSP; HIV-1: elite control v viremic control v progression.
Mentions: HLA Associations. Surprisingly, although associations between particular HLA class I molecules and clinical outcome are highly significant, the fraction of variation in outcome that can be explained by HLA alleles is rather small (Figure 3), though this does increase by a factor of 2–4 in KIR2DL2+ individuals. Clearly, HLA associations tell us about differences in HLA molecules, so a small explained fraction does not necessarily mean CD8+ T cell responses are unimportant; it could be that all CD8+ T cell responses are rather similar regardless of their restriction. However, it does caution us that we should not assume that the CD8+ T cell response is important just because HLA associations are highly significant. Furthermore, it implies that the majority of between-individual variation in clinical outcome is unlikely to be due to differences in HLA class I genotype.

Bottom Line: Multidisciplinary techniques, in particular the combination of theoretical and experimental immunology, can address questions about human immunity that cannot be answered by other means.From the turnover of virus-infected cells in vivo, to rates of thymic production and HLA class I epitope prediction, theoretical techniques provide a unique insight to supplement experimental approaches.Here we present our opinion, with examples, of some of the ways in which mathematics has contributed in our field of interest: the efficiency of the human CD8+ T cell response to persistent viruses.

View Article: PubMed Central - PubMed

Affiliation: Section of Immunology, Imperial College School of Medicine, London, United Kingdom.

ABSTRACT
Multidisciplinary techniques, in particular the combination of theoretical and experimental immunology, can address questions about human immunity that cannot be answered by other means. From the turnover of virus-infected cells in vivo, to rates of thymic production and HLA class I epitope prediction, theoretical techniques provide a unique insight to supplement experimental approaches. Here we present our opinion, with examples, of some of the ways in which mathematics has contributed in our field of interest: the efficiency of the human CD8+ T cell response to persistent viruses.

Show MeSH
Related in: MedlinePlus