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2 Regions1
Institut de Génétique et de Biologie Moléculaire et Cellulaire, Illkirch, Strasbourg, France
Some TCR variable regions are preferentially expressed in
CD4+ or CD8+ T cells, reflecting a predilection
for interacting with MHC class II or class I molecules. The molecular
basis for MHC class bias has been studied previously, in particular for
V
3 family members, pointing to a dominant role for two amino acid
positions in complementary-determining regions (CDRs) 1 and 2. We have
evaluated the generality of these findings by examining the MHC class
bias of V2 family members, an attractive system because it shows
more variability within the CDR1 and -2, exhibits variation in the
framework regions, and includes a member for which the crystal
structure has been determined. We find that preferential recognition of
MHC class I or II molecules does not always depend on residues at the
same positions of CDR1 and -2; rules for one family may be reversed in
another. Instead, there are multiple influences exerted by various
CDR1/2 positions as well as the CDR3s of both the TCR - and TCR
-chains.
1 This work was supported by institute funds from the Institut National de la Santé et de la Recherche Médicale, the Centre National de la Recherche Scientifique, the Hôpital Universitaire de Strasbourg, Bristol-Myers Squibb, and a grant (to C.B. and D.M.) from the Association pour la Recherche sur le Cancer. M.C.-N. was funded by the Portuguese Gulbenkian Ph.D. Program in Biology and Medicine and the Fundação para a Ciência e Tecnologia in Portugal.
2 Address correspondence and reprint requests to Dr. Christophe Benoist or Dr. Diane Mathis, Institut de Génétique et de Biologie Moléculaire et Cellulaire, BP 163, 67404 Illkirch Cedex, France. E-mail address: cbdm{at}igbmc.u-strasbg.fr
3 Abbreviations used in this paper: CDR, complementary-determining region; B6, C57BL/6; FR, framework region; LN, lymph node; tg, transgenic.
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