Increased Sensitivity of Antigen-Experienced T Cells through the Enrichment of Oligomeric T Cell Receptor Complexes
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Summary

Although memory T?cells respond more vigorously to stimulation and they are more sensitive to low doses of antigen than naive T?cells, the molecular basis of this increased sensitivity remains unclear. We have previously shown that the T?cell receptor (TCR) exists as different-sized oligomers on the surface of resting T?cells and that large oligomers are preferentially activated in response to low antigen doses. Through biochemistry and electron microscopy, we now showed that previously stimulated and memory T?cells have more and larger TCR oligomers at the cell surface than their naive counterparts. Reconstitution of cells and mice with a point mutant of the CD3¦Æ subunit, which impairs TCR oligomer formation, demonstrated that the increased size of TCR oligomers was directly responsible for the increased sensitivity of antigen-experienced T?cells. Thus, we?propose that an ¡°avidity maturation?mechanism underlies T?cell antigenic memory.

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