Abstracts (complete list) - Wissenschaft Online

Fabien Agenes, Jean-Pierre Dangy, Jörg Kirberg
Peripheral inter-clonal competitiveness requires T cell
receptor contact to restricting MHC molecules
In the adult, peripheral lymphocyte numbers are relatively constant, indicating that
there are homeostatic control mechanisms. Known requirements for peripheral T cell
survival, as well as homeostatic proliferation, are the TCR interaction with restricting
self-MHC molecules and the availability of lymphokines, such as IL-7. It is possible that
by competition towards these factors T cells reach a constant steady state number;
however, the mechanisms by which these restrains interrelate are not completely
understood.
It has been noted that upon adoptive transfer, homeostatic proliferation of donor T cells
can occur even in the full complement of host cells, provided the latter express a
different TCR. In other combinations, however, donor T cells are blocked by the
preformed presence of unrelated T cells. Thus there might be a “hierarchicalcompetitiveness”.
We find such hierarchical-competitiveness in the order OT-1 TCR >
P14-TCR > F5-TCR. As the OT-1 TCR is restricted to Kb, and the others are to Db, it
was possible to remove the OT-1 TCR ligand exclusively. Using various Kb-mutant mice
we demonstrate that proliferation of OT-1 T cells in hosts harboring P14-TCR expressing
cells, and, likewise, the competence of OT-1 T cells to block proliferation of P14-TCR
expressing cells, requires OT-1 TCR binding to Kb. Detecting no functional crossreactivity
of the OT-1 TCR, this excludes that direct competition for MHC molecules
causes hierarchical-competitiveness. Furthermore, parabiosis experiments with Kbmutant
mice exclude that the hierarchical-competitiveness is caused by competition for
direct cellular contact to, or modulation of, the restricting MHC-bearing cells. Thus, it is
the apparent avidity of the TCR to restricting MHC molecules that defines a relative
competence to compete, secondarily, for a trophic resource available in limited supply
and not bound to the APC. Such mechanism would allow for a localized competitiveness
operating beyond a T cells’ specificity.