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

Abstract

Although memory Tcells respond more vigorously to stimulation and they are more sensitive to low doses of antigen than naive Tcells, the molecular basis of this increased sensitivity remains unclear. We have previously shown that the Tcell receptor (TCR) exists as different-sized oligomers on the surface of resting Tcells 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 Tcells 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 Tcells. Thus, wepropose that an "avidity maturation" mechanism underlies Tcell antigenic memory.