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-Chains Pair with Diverse TCR ß-Chains1
Department of Immunology, Duke University Medical Center, Durham, NC 27710
Ag-driven selection mediates effective T cell help and the
development of Th cell memory in vivo. To analyze the dynamics of
interclonal competition during the selection process in vivo, we use
the I-Ek-restricted murine response to pigeon cytochrome
c (PCC). The dominant PCC-specific clonotype expresses
V
11Vß3 V regions with preferred sequence features in the third
hypervariable regions (CDR3). In the current study we define and
quantitatively monitor four subdominant PCC-specific clonotypes that
express V11 paired with non-Vß3 TCR ß-chains (Vß6,
Vß8.1/8.2, Vß8.3, and Vß14). The subdominant clonotypes emerge
with similar dynamics to the dominant clonotype and together amount to
similar numbers as the dominant clonotype in vivo. These subdominant
clonotypes do not efficiently enter germinal centers, although they
enter the memory compartment and rapidly re-emerge upon secondary
challenge. Analysis of CDR3 diversity in the TCR -chains identifies
many preferred sequence features expressed by the dominant clonotype.
These studies quantitatively demonstrate selection for diverse Th cells
in vivo and highlight TCR -chain dominance in Ag-driven selection
for best fit.
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