Polymorphisms and diversity of T-cell receptor-? proteins expressed in mouse spleen

Abstract

Bulk populations of T-cell receptor (Tcr) gamma delta-expressing splenocytes from different inbred strains of mice were examined for the diversity of Tcr gamma delta proteins. Immunoprecipitations with anti-C gamma 1/2, anti-C gamma 4, and anti-V gamma 1 sera demonstrated that splenocytes from B10.BR, C57BL/6, and C57L strains of mice expressed the same array of Tcr gamma proteins, namely V gamma 1-C gamma 2, V gamma 1-C gamma 4, and V gamma 2-C gamma 1, although the Tcr gamma delta heterodimers observed for each of these strains were biochemically distinct. Examination of bulk splenic Tcr gamma delta heterodimers from several other inbred strains of mice demonstrated that each of the strains could be categorized into one of three basic phenotypes. For several reasons, the differences observed between the strains appeared to be solely dependent on polymorphisms of the Tcrg loci. First, F1 mice co-expressed both parental Tcr gamma delta phenotypes. Second, the distinguishing polymorphism between mice of phenotype 1 and phenotypes 2 or 3 was due to the presence of an N-linked glycosylation site within the Tcrg-Cl gene segment, previously described for BALB.B and C57BL/6 Tcrg-Cl genes. Finally, the V gamma 1-C gamma 4 polymorphism between mice of phenotype 3 and phenotypes 1 or 2 was due to differences in core protein size. Furthermore, the three defined Tcr gamma chains were expressed independently of the major histocompatibility complex (MHC) haplotype. Although no striking qualitative differences in Tcr gamma delta heterodimers were observed between strains (including those with autoimmune disorders), a quantitative difference in the relative amount of C gamma 4-encoded proteins was observed on Tcr gamma delta splenocytes from both newborn euthymic and adult athymic mice when compared to adult Tcr gamma delta splenocytes from euthymic mice. These results demonstrate that genetic polymorphisms exist among different mouse strains and suggest that selective developmental pressures may govern Tcr gamma delta expression.