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.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

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.

Int Immunol. 1999 Mar;11(3):435-44. Unique Identifier : AIDSLINE MED/99236844
Herrmann T; Hofmann K; Nagel NE; Asmuss A; Hunig T; Wonigeit K; Institut fur Virologie und Immunobiologie,; Julius-Maximillians-Universitat Wurzburg, Germany.; herrmann-t@vim.uni-wuerzburg.de

Abstract: Different rat Tcrb haplotypes express either TCR beta 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 CDR2beta to highly conserved areas of C-terminal parts of the alpha helices of class I MHC molecules.

Keywords: JOURNAL ARTICLE Alleles Animal Cell Differentiation Crosses, Genetic CD4-Positive T-Lymphocytes/CYTOLOGY/*IMMUNOLOGY CD8-Positive T-Lymphocytes/CYTOLOGY/*IMMUNOLOGY Female Haplotypes Histocompatibility Antigens Class I/GENETICS/IMMUNOLOGY Major Histocompatibility Complex/*IMMUNOLOGY Models, Immunological Rats Rats, Inbred Strains Receptors, Antigen, T-Cell, alpha-beta/*GENETICS Support, Non-U.S. Gov't T-Lymphocyte Subsets/CYTOLOGY/*IMMUNOLOGY Thymus Gland/CYTOLOGY/*IMMUNOLOGY Variation (Genetics)
990930
A9991309

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