How could broad T-cell response work under low antigen expression?
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How broad Tcell response could work under low an3gen expression Tetsuo Tsukamoto CEA/FontenayauxRoses, France (Presented on 20120829 in ICARIS2012, Taormina, Italy)
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A talk about a possible mechanism in which broad T-cell response recognizing various different epitopes could act quickly to detect virus-infected cells in the very early phase of infection when antigen expression is still limited.
Transcript of How could broad T-cell response work under low antigen expression?
How broad T-‐cell response could work under low an3gen expression
Tetsuo Tsukamoto
CEA/Fontenay-‐aux-‐Roses, France
(Presented on 2012-‐08-‐29 in ICARIS2012, Taormina, Italy)
My specializa3on
• Development of AIDS vaccines which could induce HIV-‐specific CD8+ T-‐cell response
• Analysis on the role of CD4+ and CD8+ T-‐cell response in HIV pathogenesis
Objec3ve
• To show a hypotheses that broad CD8+ T-‐cell response could act quickly in the early phase of infecTon
Imagine a close-‐packed structure…
There are up to 12 cells around one.
Viral replica3on & suppression model
Viral replica3on & suppression model
How is P determined?
Killing rate (P)
Only part of surrounding CTLs are s3mulated when an3gen expression is limited
Number of S3mulated CTLs (K) for a single CTL popula3on
Provided that
When epitope levels on infected cells are very low, broader T-‐cell response could be more sensi3ve, or in
other words could act more quickly
Number of S3mulated CTLs (K) for mul3ple CTL popula3ons (simplified)
Provided that CTLs consist of n different populations with the same numbers of cells, and with the same properties except for the antigen (epitope) specificity,
Viral loads with different numbers of CTL popula3ons (T-‐cell expansion is not considered here)
n=0 n=1 n=2
n=4 n=6
––– T (total target cells), ––– I (infected cells), ––– V (viral load)
Indica3ons
• The hypothesis tells that mulTple CTL populaTons could act more quickly in the iniTal phase of HIV infecTon than a single CTL populaTon.
• It also tells that the breadth of CTL response could support long-‐term unsterile virus control in which plasma viral load is limited to an undetectable level.
• The idea is consistent with a previously shown hypothesis by Scherer et al (2006) on T-‐cell immunodominance formaTon telling that lower anTgen expression in APCs could lead to broader T-‐cell response.
A possible design of the T-‐cell immune system
• T-‐cell compeTTon and cooperaTon could possibly lead to higher sensiTviTes to limited amount of anTgens (i.e. limited amount of informaTon)
TODOs
• To design a real experiment, possibly in vitro at first. • For this purpose we would need mulTple (hopefully 6) Gag-‐specific CTL populaTons.
• We would also need a CD4+ target cell culture (or cell line) which expresses all MHC class I alleles required.
