Ka. Hogquist et al., POSITIVE SELECTION OF CD8-CELLS INDUCED BY MAJOR HISTOCOMPATIBILITY COMPLEX BINDING PEPTIDES IN FETAL THYMIC ORGAN-CULTURE( T), The Journal of experimental medicine, 177(5), 1993, pp. 1469-1473
We have used an in vitro system to study the effects of major histocom
patibility complex class I binding peptides on thymic development. Fet
al thymus lobes from mice deficient in the class I light chain (beta2
microglobulin or beta2M-/-) were cultured for 10 d in vitro, during wh
ich time T cell precursors develop into mature T cells. In these organ
cultures, as in the adult or neonatal beta2M-/- thymus, CD8+ mature T
cells did not develop, demonstrating that the mature T cells seen dur
ing early murine thymic development are the result of the positive sel
ection process. To these cultures we added various class I binding pep
tides with or without a source of exogenous beta2M. CD8+ T cells devel
oped to various degrees only in the presence of beta2M and peptides. U
sing peptide mixtures of differing complexity, we showed that the effi
ciency of this process is dependent more on peptide complexity than on
peptide concentration. These data argue for a specific role for pepti
des in the process of positive selection. Furthermore, this culture sy
stem should be useful in identifying peptides that can promote positiv
e selection of cells expressing a specific T cell receptor (TCR) in TC
R transgenic mice.