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

SummaryAlthough 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.

Graphical AbstractFigure optionsDownload high-quality image (104 K)Download as PowerPoint slideHighlights
► Previously stimulated and memory T cells are enriched for oligomeric TCR complexes
► Oligomeric TCR complexes enrichment correlates with increased antigen sensitivity
► Genetic impairment of oligomeric TCRs formation reduces antigen sensitivity
► Oligomeric TCR formation depends on the transmembrane region of CD3?