POSITIVE SELECTION OF CD8-CELLS INDUCED BY MAJOR HISTOCOMPATIBILITY COMPLEX BINDING PEPTIDES IN FETAL THYMIC ORGAN-CULTURE( T)

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.