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The Journal of Immunology, 2002, 168: 3801-3807.
Copyright © 2002 by The American Association of Immunologists

A Molecular Marker for Thymocyte-Positive Selection: Selection of CD4 Single-Positive Thymocytes with Shorter TCRB CDR3 During T Cell Development1

Maryam Yassai*, Kristin Ammon*, Joan Goverman{dagger}, Phillipa Marrack{ddagger}, Yuri Naumov* and Jack Gorski2,*

* Blood Research Institute, Blood Center of Southeastern Wisconsin, Milwaukee, WI 53201; {dagger} Department of Immunology, University of Washington, Seattle, WA 98105; and {ddagger} Howard Hughes Medical Institute, National Jewish Medical and Research Center, Denver, CO 80206

The generation of the naive T cell repertoire is a direct result of maturation and selection events in the thymus. Although maturation events are judged predominantly on the expression of surface markers, molecular markers, more intimately involved in the selection process, can be informative. We have identified a molecular marker for selection in later stages of maturation in humans. Thymocytes are selected for the expression of TCR {beta}-chains with shorter CDR3 at the double-positive to single-positive (SP) transition. Here we extend these studies to the mouse and show that the selection phenotype is not related to {alpha}-chain pairing but is a function of the MHC haplotype. Interestingly, the selection is much more apparent in CD4 SP thymocytes than in CD8 SP cells. This is in contrast to human thymocytes, where the selection is equally apparent in both lineages. The involvement of MHC in the process argues that this is a positive selection stage. The difference in the extent of this selection between the two SP lineages may indicate a class difference in the nature of the TCR-MHC interaction, the role of coreceptors in the selection process, or both.




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