An exact comparison between the efficiency of two‐ and three‐cell‐type clusters in mediating helper activity

Abstract

Adoptive transfer of anti-H-2Db-primed B cells combined with anti-minor histocompatibility antigen-primed T cells enables the effect of linked and unlinked alloantigen to be compared. Over an extensive dose range the unlinked antigen proved ineffective. In a previously described, exactly comparable system for assessing the same effect on cytotoxic T cell precursors, low doses of linked antigen had proved approximately equally effective, but high doses of unlinked antigen had proved effective. This contrast supports the hypothesis that whereas T-B collaboration is mediated by two-cell-type clusters, collaboration between T cells requires formation of three-cell-type clusters.

Identification of thyroid stimulating hormone receptor-specific T cells in Graves' disease thyroid using autoantigen-transfected Epstein-Barr virus-transformed B cell lines.

“…It was unclear, however, whether these findings were due to the absence of TSHR-specific T cells in that patient alone or in Graves' disease per se. The presence of TSHR autoantibodies might be explicable on the basis of "intermolecular help" of TSHR-specific B cells by TPO-specific T cells, since TSHR and TPO are "linked molecules" by virtue of their coexpression on TEC (7).…”

Substrate-bound CCL21 and ICAM1 combined with soluble IL-6 collectively augment the expansion of antigen-specific murine CD4+ T cells

“…Following activation, T cells begin to proliferate and aggregate to form cell clusters around antigen-presenting DCs. [38][39][40] Within these clusters, both T-DC and T-T bonds are forged and mediated through the immobilization of ICAM1 and lymphocyte functionassociated 1 (LFA1). 38,39 By binding to its CC-chemokine receptor 7 (CCR7) on T cells, CCL21 increases LFA1 responsiveness to ICAM1 and mediates the arrest of motile lymphocytes on ICAM1-expressing DCs, endothelial cells, and other T cells.…”

“…[38][39][40] Within these clusters, both T-DC and T-T bonds are forged and mediated through the immobilization of ICAM1 and lymphocyte functionassociated 1 (LFA1). 38,39 By binding to its CC-chemokine receptor 7 (CCR7) on T cells, CCL21 increases LFA1 responsiveness to ICAM1 and mediates the arrest of motile lymphocytes on ICAM1-expressing DCs, endothelial cells, and other T cells. 30,41 On the basis of the central role of CCL21 and ICAM1 in mediating efficient T-DC and T-T interactions, we hypothesized they could also be exploited in a "minimal," yet effective, synthetic environment to modulate intercellular interactions and improve expansion of antigen-specific T cells.…”

Three-Cell Interactions in T Cell-Mediated Suppression? A Mathematical Analysis of Its Quantitative Implications

“…Mechanisms of interaction involving the formation of conjugates of more than two cell types have been postulated previously (31), the major example being the classical view of linked recognition of Ag aby CD4 and CD8 T cells and their cooperation. It has been argued (32,33) that such interaction imposes strong constraints on the efficiency of the process where it is imbedded due to the relatively low frequency of its rate-limiting event, the simultaneous encounter between more than two cells. This straightforward quantitative prediction provides an easy way to test the involvement of multicellular conjugates in suppression.…”