The TCRBJ and TCRBV repertoire in naive and memory human T-cells

Cowan, Teresa (1997) The TCRBJ and TCRBV repertoire in naive and memory human T-cells. Masters thesis, Memorial University of Newfoundland.

[English] PDF (Migrated (PDF/A Conversion) from original format: (application/pdf)) - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. Download (22MB) [English] PDF - Accepted Version Available under License - The author retains copyright ownership and moral rights in this thesis. Neither the thesis nor substantial extracts from it may be printed or otherwise reproduced without the author's permission. (Original Version)

Abstract

Previous studies suggested that human memory and naive T-cells can be distinguished based on the differential expression of two CD45 isoforms. It was believed that CD45RA is expressed only on naive cells and that CD45RO is expressed only on memory cells. The separation of cell subsets based on the differential expression of CD45 isoforms was fundamental to the experimental design used to test the hypotheses presented in this thesis. -- The first hypothesis was that the memory T-cell TCRBJ and TCRBV repertoires are significantly different from those of naive T-cells within the same individual. Using a quantitative RT-PCR technique, it was found that the TCRBJ, and to a lesser extent, TCRBV repertoires of CD45RA$\sp+$ (naive) and CD45RO$\sp+$ (memory) T-cells differ. -- The second hypothesis was that genetics and, more precisely, HLA affect the TCRBJ repertoire of CD4$\sp+$CD45RO$\sp-$ (naive) T-cells. By comparing the naive T-cell TCRBJ repertoires of identical twins and unrelated individuals and by employing a novel method of statistical analysis, statistical evidence was found for a genetic effect on the TCRBJ repertoire of CD4$\sp+$CD45RO$\sp-$ (naive) T-cells. Similarly, family studies provided statistical evidence for an HLA effect on the CD4$\sp+$CD45RO$\sp-$ (naive) T-cell TCRBJ repertoire in comparisons of HLA identical and HLA non-identical siblings. -- Statistical evidence was obtained in support of the third hypothesis which was that twin pairs discordant for multiple sclerosis (MS) have less similar CD4$\sp+$CD45RO$\sp-$ (naive) T-cell TCRBJ repertoires than do healthy twin pairs. -- It appears some CD45RO$\sp+$ (memory) T-cells may revert to the expression of the CD45RA (naive) isoform and retain their immunological memory. These results, however, do not affect the interpretation of results for the first hypothesis, and results obtained for HLA identical vs. HLA non-identical siblings suggest that the effect of "revertant" cells was minimal.

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