J. Zerrahn et al., Class I MHC molecules on hematopoietic cells can support intrathymic positive selection of T cell receptor transgenic T cells, P NAS US, 96(20), 1999, pp. 11470-11475
Citations number
32
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
The identity of cells that mediate positive selection of CD8(+) T cells was
investigated in two T cell receptor (TCR) transgenic systems. Irradiated b
eta(2)-micro-globulin mutant mice or mice with mutations in both the K-b an
d D-b genes were repopulated with fetal liver cells from class I+ TCR trans
genic mice, In the case of the 2C TCR, mature transgene-expressing CD8(+) T
cells appeared in the thymuses of the chimeras and in larger numbers in th
e peripheral lymphoid organs. These CD8(+) T cells were functional, exhibit
ed a naive, resting phenotype, and were mostly thymus-dependent. Their deve
lopment depended on donor cell class I expression. These results establish
that thymic hematopoietic cells can direct positive selection of CD8(+) T c
ells expressing a conventional TCR, In contrast, no significant development
of HY (male antigen)-TCR+ CD8(+) T cells was observed in class I+ into cla
ss I-deficient chimeras. These data suggest that successful positive select
ion directed by hematopoietic cells depends on specific properties of the T
CR or its thymic ligands, The possibility that hematopoietic cell-induced,
positive selection occurs only with TCRs that exhibit relatively high avidi
ty interactions with selecting ligands in the thymus is discussed.