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

Rashmi Kumar, María Ferez, Mahima Swamy, Ignacio Arechaga, María Teresa Rejas, Jose M. Valpuesta, Wolfgang W.A. Schamel, Balbino Alarcon, Hisse M. van Santen (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

115 Citations (Scopus)

Abstract

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 CD3ζ 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.

Original languageEnglish
Pages (from-to)375-387
Number of pages13
JournalImmunity
Volume35
Issue number3
DOIs
Publication statusPublished - 23 Sep 2011

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