Variability in T cell receptor V beta gene usage in human peripheral blood lymphocytes. Studies of identical twins, siblings, and insulin-dependent diabetes mellitus …

U Malhotra, R Spielman… - Journal of immunology …, 1992 - journals.aai.org
U Malhotra, R Spielman, P Concannon
Journal of immunology (Baltimore, Md.: 1950), 1992journals.aai.org
Recent studies focused on the diversity and molecular organization of the human TCR-beta
complex have begun to establish the genetic basis for the potential repertoire of V beta
specificities in T cells. The scope and variability of the actual repertoire derived from this
potential repertoire, however, remains to be clarified. In this study, V beta usage by human
peripheral T cells derived from serial samples of the same individual, identical twins, and the
members of three nuclear families that include four members with insulin-dependent …
Abstract
Recent studies focused on the diversity and molecular organization of the human TCR-beta complex have begun to establish the genetic basis for the potential repertoire of V beta specificities in T cells. The scope and variability of the actual repertoire derived from this potential repertoire, however, remains to be clarified. In this study, V beta usage by human peripheral T cells derived from serial samples of the same individual, identical twins, and the members of three nuclear families that include four members with insulin-dependent diabetes mellitus (IDDM) was assessed by both quantitative polymerase chain reaction and Northern blotting with V beta subfamily-specific probes. Samples taken from the same individual over a period of 21 months and analyzed in separate experiments indicated stability in the peripheral repertoire, whereas the similarity in peripheral V beta usage in a pair of identical twins suggested a strong role for genetics in shaping the peripheral T cell repertoire. In contrast, V beta usage in siblings and in unrelated individuals was observed to differ substantially. In particular, peripheral expression of V beta 3 and V beta 20 differed by more than sixfold among members of two different families. Segregation analysis of TCR and HLA haplotypes in these families suggested that variation in V beta 20 expression was TCR haplotype specific. Subsequent nucleotide sequence analysis of the V beta 20 gene segment in multiple members of these families revealed the presence of a null allele for V beta 20 expression. No consistent significant differences in V beta usage were observed in IDDM patients relative to their siblings or between identical twins discordant for IDDM. These results suggest that the repertoire of peripheral T cell specificities present in different individuals in human populations varies dramatically because of the effects of multiple factors, including TCR germ-line polymorphism.
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