Multiple factors shape the TCR Vβ repertoire in humans

Daniel, Enoch S. (1995) Multiple factors shape the TCR Vβ repertoire in humans. Masters thesis, Memorial University of Newfoundland.

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Abstract

Contributions to the human peripheral TCR Vβ repertoire were assessed by a semi-quantitative PCR method. Lymphocytes were expanded by PHA using a stimulation protocol that did not alter the Vβ repertoire. Marked differences in PCR-priming efficiencies of 23 Vβ segments were identified. Significant correlations between priming efficiencies and the observed Vβ repertoire were found and therefore the data were corrected for differences in priming efficiencies. Vigorous statistical analysis showed that non-genetic factors were responsible for significant differences between total T cell Vβ repertoires of monozygotic twin pairs and unrelated pairs. In preliminary analysis, however these influences were misinterpreted as having a genetic basis. No evidence was obtained that genetics (including HLA) influenced the total T cell Vβ repertoires. However, the role of genetics in influencing the Vβ repertoire of CD4⁺ or CD8⁺ T cell subsets could be detected at the level of a few Vβs. -- Large families were studied to delineate the effects of HLA on the TCR Vβ repertoire. The results of these studies indicated that HLA influenced the Vβ repertoire but that non-HLA factors also have a significant influence. -- Further, it was found that particular Vβs (15,16,18) were expressed at a constant level and several Vβs (particularly 10 and 12) were typically highly variable in expression levels. This was true for all individuals irrespective of the genetic background (including HLA) and irrespective of the T cell type. Still other Vβs tended to be highly variable in expression in CD4⁺ or CD8⁺ subsets but not in both. -- These studies unequivocally document that influences on the Vβ repertoires are complex. Genetics including HLA seem to play a role, however non-genetic influences can also have a major role in determining the TCR Vβ repertoire.

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