Clonal selection of helper T cells is determined by an affinity threshold with no further skewing of TCR binding properties
- PMID: 15539153
- DOI: 10.1016/j.immuni.2004.09.008
Clonal selection of helper T cells is determined by an affinity threshold with no further skewing of TCR binding properties
Abstract
Helper T cell responses that focus the TCR repertoire of responding clones provide experimental access to the mechanisms of clonal selection in vivo. Using TCRbeta chain animals, we directly evaluate the extent of TCRalpha CDR3 diversity and the pMHCII binding attributes of individual antigen-specific Th cells. Here, we demonstrate that dominant clonotypes, as defined by TCR junctional sequence similarities, are surprisingly diverse at the level of pMHCII binding properties, before and after antigen exposure. During an immune response, we can detect and quantify the selective loss of antigen-specific clonotypes that express lower-affinity TCR. This affinity threshold selection is followed by the unbiased propagation of preferred clonotypes regardless of TCR-pMHCII half-lives or affinity. Thus, an affinity threshold mechanism discriminates Th clones with TCR of best fit and propagates clonal diversity without promoting autoreactivity.
Comment in
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Antigen-driven T cell expansion: affinity rules.Immunity. 2004 Nov;21(5):603-4. doi: 10.1016/j.immuni.2004.11.001. Immunity. 2004. PMID: 15539146
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