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Publication : The multigenic structure of the MHC locus contributes to positive selection efficiency: a role for MHC class II gene-specific restriction.

First Author  Monteiro MC Year  2005
Journal  Eur J Immunol Volume  35
Issue  12 Pages  3622-30
PubMed ID  16259007 Mgi Jnum  J:113773
Mgi Id  MGI:3687632 Doi  10.1002/eji.200535190
Citation  Monteiro MC, et al. (2005) The multigenic structure of the MHC locus contributes to positive selection efficiency: a role for MHC class II gene-specific restriction. Eur J Immunol 35(12):3622-30
abstractText  The study of T cell positive selection in the thymus has long been focused on the specificity of the MHC-TCR interactions, making use of genetically manipulated mice that display TCR specificities or selecting peptides of limited diversity. However, little is known on the role of the MHC molecules irrespective of the peptide specificity and the implications of MHC multigenic structure in thymic positive selection have not been addressed. Here, we investigated the effect of MHC class II genetic configuration on the positive selection efficiency of naturally generated pre-selection repertoires in the mouse thymus. Analysis of positively selected thymocyte populations in MHC-congenic and -transgenic mice revealed that expression of I-E molecule in the thymic cortex increases positive selection efficiency of CD4 cells by approximately 50%. We show that increments in positive selection attributable to either the I-A and I-E genes are not due to increased MHC class II expression in the thymic cortex and are not affected by the number of MHC alleles. Collectively, our findings imply that MHC class II gene-restricted TCR specificities significantly contribute to positive selection efficiency, introducing the notion that multigenic structure of the MHC locus serves to increase selection of non-overlapping TCR repertoires.
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