International Immunology, Vol 9, 1385-1391, Copyright © 1997 by Oxford University Press
Y Fukui, K Yamamoto, T Koga, K Yamane and T Sasazuki
To address whether expression of the relevant MHC molecules on thymic
epithelial cells (TEC) is sufficient for positive selection, the fate of
CD4+ T cells directed by the DR alpha E beta b molecule was compared
between two lines of HLA-DRA transgenic mice, DR alpha-24 expressing DR
alpha E beta b on TEC and hematopoietic cells, and DR alpha-30 expressing
the molecule on TEC but not on other cell lineages. CD4+ T cells were
selected to mature on DR alpha E beta b molecules in both lines deficient
for the endogenous MHC class I and class II molecules, whereas CD4+ T cell
differentiation in DR alpha-30, as compared with that in DR alpha-24, was
severely impaired when these mice were crossed with mice transgenic for the
DR alpha E beta b-restricted alpha beta TCR. In contrast, CD4+ T cells
expressing the same TCR alpha beta as the transgenes were selected to
mature in DR alpha-30 crossed with the single TCR beta transgenic mice.
Taken together, these results indicate that the restricted expression of DR
alpha E beta b on TEC is sufficient for positive selection in the TCR beta
and non-TCR transgenic mice, but the expression on both TEC and
hematopoietic cells is required for that in the TCR alpha beta transgenic
mice. In the light of the difference in the developmental stage at which
alpha beta TCR are expressed between TCR alpha beta and TCR beta transgenic
mice, the interaction of the TCR alpha beta with DR alpha E beta b
molecules expressed on hematopoietic cells required for positive selection
in TCR alpha beta transgenic mice could be mapped to the early stage of T
cell differentiation and might mimic 'undefined' early signaling of
thymocytes in physiological T cell differentiation.
ARTICLES
Differential requirement of MHC class II molecules expressed on hematopoietic cells for positive selection of CD4+ thymocytes in TCR alpha beta and TCR beta transgenic mice
Department of Genetics, Kyushu University, Fukuoka, Japan.
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