CD4+ T Cells Mature in the Absence of MHC Class I and Class II Expression in Ly-6A.2 Transgenic Mice.
The TCRs expressed on T lymphocytes recognize foreign peptides bound to MHC molecules. This reactivity is the basis of specific immune response to the foreign Ag. How such specificities are generated in the thymus is still being debated. Signals generated through TCR upon interaction with self MHC-peptide complexes are critical for maturation of the CD41 helper and CD81 cytotoxic subsets. We have observed maturation of CD41 but not CD81 T cells in Ly-6A.2 transgenic MHC null mice. Since there can be no interactions with MHC molecules in these mice, these CD41 cells must express the T cell repertoire that exists before positive and negative selection. Interestingly, despite an absence of selection by MHC molecules, the CD41 cells that mature recognize MHC molecules at a frequency as high as in CD41 cells in normal mice. These results demonstrate that: 1) the germline sequences encoding TCRs are biased toward reactivity to MHC molecules; and 2) CD41 cells as opposed to CD81 cells have distinct lineage commitment signals. These results also suggest that signals originating from Ly-6 can promote or substitute for signals generated from TCR that are required for positive selection. Moreover, this animal model offers a system to study T cell development in the thymus that can provide insights into mechanisms of lineage commitment in developing T cells.
|Main Author:||Henderson, S. Christine.|
|Other Authors:||Berezovskaya, Alla., English, Andrea., Palliser, Deborah., Rock, Kenneth L., Bamezai, Anil.|