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Publication : Control of TCR V alpha-mediated positive repertoire selection and alloreactivity by differential J alpha usage and CDR3 alpha composition.

First Author  Torres-Nagel N Year  1997
Journal  Int Immunol Volume  9
Issue  10 Pages  1441-52
PubMed ID  9352349 Mgi Jnum  J:43616
Mgi Id  MGI:1098103 Doi  10.1093/intimm/9.10.1441
Citation  Torres-Nagel N, et al. (1997) Control of TCR V alpha-mediated positive repertoire selection and alloreactivity by differential J alpha usage and CDR3 alpha composition. Int Immunol 9(10):1441-52
abstractText  In rats expressing the f allele of the rat MHC (RT1f), CD8 T cells utilizing the V alpha 8.2 segment are 10-fold overselected during thymic development, resulting in V alpha 8.2 expression by 14% of mature CD8 T cells as compared to 1-2% in MHC congenic strains. In the alloreactive responses of CD8 T cells from RT1f-negative rats against RT1f, V alpha 8.2+ CD8 T cells are also preferentially expanded. Neither overselection nor alloreactivity of V alpha 8.2+ TCR require selective V beta pairing. However, RT1f alloreactive V alpha 8.2+ TCR preferentially use a related set of J alpha segments which contribute short homogeneous CDR3 alpha loops, with features suggesting peptide promiscuity, and little N additions. In contrast, only few overselected V alpha 8.2+ CD8 T cells showed an imprint of positive selection on J usage or CDR3 composition. The results demonstrate that a single V alpha segment can promote both MHC allele-specific positive selection and alloreactivity, and that the latter is more dependent on an additional contribution of CDR3 alpha, possibly by promoting reactivity with a diverse set of MHC-bound peptides or by providing additional MHC contacts.
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