Development of the T Cell Repertoire: Contributions of Both TCR-MHC and Accessory Molecule-MHC Interactions
To examine the issue of thymic selection with experimental systems entirely different from hematopoietic and thymic chimeras, the development of the T cell repertoire has been analyzed under conditions where expression of MHC- encoded gene products is blocked by in vivo mAb treatment during the early post-natal period. Such experiments also serve to re-evaluate in normal mice whether positive selection in the context of thymic MHC indeed forms the basis for the phenomenon of MHC restriction. The initial results demonstrated that blocking of class ll-MHC resulted in abrogation of development of CD4+CD8- T cells (Kruisbeek et al 1985), and blocking of class l-MHC prevented generation of CD4-CD8+ T cells (Marusic- Galesic et al 1988). Thus, the impressively strong correlation, in mature T cells, between expression of particular accessory molecules (CD4 or CD8) and MHC- restriction specificity (class II or class I, respectively) (Swain 1983) appears to reflect early selection events. These findings are consistent with the idea that blocking of the appropriate MHC molecules prevents delivery of a positive signal necessary for clonal differentiation.
KeywordsCell Repertoire Accessory Molecule Thymic Selection Single Positive Cell Encode Gene Product
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