Antigen-driven selection of TCR in vivo: related TCR alpha-chains pair with diverse TCR beta-chains

Ag-driven selection mediates effective T cell help and the development of T h cell memory in vivo. To analyze the dynamics of interclonal competition d uring the selection process in vivo, me use the I-E-k-restricted murine res ponse to pigeon cytochrome c (PCC), The dominant PCC-specific clonotype exp resses V alpha 11V beta 3 V regions with preferred sequence features in the third hypervariable regions (CDR3). In the current study we define and qua ntitatively monitor four subdominant PCC-specific clonotypes that express V alpha 11 paired with non-V beta 3 TCR beta-chains (V beta 6, V beta 8.1/8. 2, V beta 8.3, and V beta 14), The subdominant clonotypes emerge with simil ar dynamics to the dominant clonotype and together amount to similar number s as the dominant clonotype in vivo, These subdominant clonotypes do not ef ficiently enter germinal centers, although they enter the memory compartmen t and rapidly re-emerge upon secondary challenge, Analysis of CDR3 diversit y in the TCR alpha-chains identifies many preferred sequence features expre ssed by the dominant clonotype, These studies quantitatively demonstrate se lection for diverse Th cells in vivo and highlight TCR alpha-chain dominanc e in Ag-driven selection for best fit.