International Immunology, Vol 9, 1441-1452, Copyright © 1997 by Oxford University Press
N Torres-Nagel, A Deutschlander, T Herrmann, B Arden and T Hunig
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.
ARTICLES
Control of TCR V alpha-mediated positive repertoire selection and alloreactivity by differential J alpha usage and CDR3 alpha composition
Institute for Virology and Immunobiology, University of Wurzburg, Germany.
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