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

TY - JOUR

T1 - Increased Sensitivity of Antigen-Experienced T Cells through the Enrichment of Oligomeric T Cell Receptor Complexes

AU - Kumar, Rashmi

AU - Ferez, María

AU - Swamy, Mahima

AU - Arechaga, Ignacio

AU - Rejas, María Teresa

AU - Valpuesta, Jose M.

AU - Schamel, Wolfgang W.A.

AU - Alarcon, Balbino

AU - van Santen, Hisse M.

PY - 2011/9/23

Y1 - 2011/9/23

N2 - 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.

AB - 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.

UR - https://www.scopus.com/pages/publications/80053132781

U2 - 10.1016/j.immuni.2011.08.010

DO - 10.1016/j.immuni.2011.08.010

M3 - Article

C2 - 21903423

AN - SCOPUS:80053132781

SN - 1074-7613

VL - 35

SP - 375

EP - 387

JO - Immunity

JF - Immunity

IS - 3

ER -