THYMIC SELECTION DEFINES MULTIPLE T-CELL RECEPTOR V-BETA REPERTOIRE PHENOTYPES AT THE CD4/CD8 SUBSET LEVEL

We describe here the use of a sensitive and accurate multiprobe VβRNase protection assay in characterizing the expression levels of 17 Vβ genes in separated CD4+ and CD8+ subsets of selected mouse strains. The IE-reactive Vβ genes (Vβs 11, 12, 5.1 and 16) showed various patterns of skewed subset expression in different strains, suggesting additional influences of IA, class I, and non-MHC genes in the selection process. Clonal deletion of Vβ11- and Vβ12-bearing T cells, among others, was skewed strongly towards the CD4+ subset in many IE+ mouse strains, supporting the notion that negative selection can cause incomplete, subset biased, Vβ clonal deletions. Broad analysis in separated CD4+ and CD8+ subsets gave improved resolution of Vβ repertoire selection, and revealed significant strain and/or subset specific skewing for additional Vβ genes; with consistent bias towards higher expression of Vβ7 and Vβ13 in the CD8+ subset, and Vβ15 in the CD4+ subset of most mouse strains. The influence of diverse non-MHC ligands in Vβ repertoire selection was further illustrated by the identification of unique Vβ repertoires for six different MHC-identical (H2(k)) strains. Such polymorphisms in TCR repertoire expression may help to define better disease susceptibility phenotypes.