International Immunology, Vol. 11, No. 3, 435-444,
March 1999
© 1999 Japanese Society for Immunology
Differential CD4/CD8 subset-specific expression of highly homologous rat Tcrb-V8 family members suggests a role of CDR2 and/or CDR4 (HV4) in MHC class-specific thymic selection
Institut für Virologie und Immunobiologie, Julius-Maximillians-Universität Würzburg, Versbacherstrasse 7, 97078 Würzburg, Germany
1 Klinik für Abdominal- und Transplantationschirurgie, Medizinische Hochschule Hannover, 30625 Hannover, Germany
Correspondence to: T. Herrmann fax: +49-931-201-2243, e-mail: herrmann-t{at}vim.uni-wuerzburg.de
Different rat Tcrb haplotypes express either TCR ß variable segment (Tcrb-V) 8.2l or 8.4a. Both V segments bind the mAb R78 but differ by one conservative substitution (L14V) and clusters of two and four substitutions in the complementarity-determining region (CDR) 2 and CDR4 [hypervariable loop 4 (HV4)]. Independently of MHC alleles numbers of R78+CD4+ cells are lower in Tcrb-V8.2l-expressing than in Tcrb-V8.4a-expressing strains. Expression of R78+ TCR during T cell development, analysis of backcross populations and generation of a Tcrb congenic strain [LEW.TCRB(AS)] define two mechanisms how Tcrb haplotypes affect the frequency of R78+ cells, one acting prior to thymic selection leading to up to 2-fold higher frequency of Tcrb-V8.4a versus Tcrb-V8.2l in unselected thymocytes and another occurring between the TCRlow and the CD4/CD8 single-positive stage. The latter leads to a 50% reduction of frequency of Tcrb-V8.4a CD8+ cells but not CD4+ cells and does not affect either subset of Tcrb-V8.2l cells. A comparison of rat classical class I MHC (RT1.A) sequences and current models of TCR–MHC–peptide interaction suggests that this reduction in frequency of Tcrb-V8.4a CD8 cells may be a consequence of differential selection of Tcrb-V8.2l versus Tcrb-V8.4a TCR by differential binding of CDR2ß to highly conserved areas of C-terminal parts of the 
helices of class I MHC molecules.
Keywords: complementarity-determining region, MHC, polymorphism, superantigens, TCR, T cell repertoire, V segments
Transmitting editor: H. R. MacDonald
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