Increased sensitivity of antigen-experienced T cells through the enrichment of oligomeric T cell receptor complexes

Immunity. 2011 Sep 23;35(3):375-87. doi: 10.1016/j.immuni.2011.08.010. Epub 2011 Sep 8.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD3 Complex / genetics
  • CD4-Positive T-Lymphocytes / immunology*
  • Cells, Cultured
  • Electrophoresis, Polyacrylamide Gel
  • Flow Cytometry
  • Humans
  • Immunoblotting
  • Immunologic Memory*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Biological
  • Oligodeoxyribonucleotides* / genetics
  • Oligodeoxyribonucleotides* / immunology
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology*


  • CD3 Complex
  • Oligodeoxyribonucleotides
  • Receptors, Antigen, T-Cell