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Department of Anatomy, University of Birmingham Medical School, Edgbaston, Birmingham, United Kingdom
In the thymus, phenotypically and functionally mature single
positive cells are generated from immature
CD4+8+ precursors by a process known as
positive selection. Although this event is known to involve 
ßTCR
ligation by peptide/MHC complexes expressed on thymic stromal cells, it
is clear that positive selection is a multistage process involving
transition through an intermediate
CD4+8+69+ phase as well as
subsequent postselection phases. By analyzing the development of
preselection CD4+8+69- and
intermediate CD4+8+69+ thymocytes
in the presence of MHC class I-deficient, MHC class II-deficient, and
MHC double-deficient thymic stromal cells, we investigated the role of
MHC molecules at three distinct points during positive selection.
Although the initiation of positive selection is critically dependent
upon MHC interactions, we find the that later stages of maturation,
involving the differentiation of CD4+8- and
CD4-8+ cells from
CD4+8+69+ thymocytes, occur in the
absence of MHC molecules. Moreover, an analysis of the postselection
proliferation of newly generated CD4+8- and
CD4-8+ thymocytes shows that this also
occurs independently of MHC molecules. Thus, our data provide direct
evidence that, although positive selection is a multistage process
initiated by TCR-MHC interactions, continuation of this process and
subsequent postselection events are independent of ongoing engagement
of the TCR.
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