HLA-dependent peripheral T cell receptor (TCR) repertoire formation and its modification by rheumatoid arthritis (RA)

Abstract

SUMMARYOur previous studies have disclosed that the peripheral T cell receptor b (TCRB) gene repertoires of RA monozygotic twins were similar. This suggested that the TCRBV repertoire is controlled primarily by genetic factors. Here, we examine how the combination of HLA and presence of RA influence the peripheral TCRB repertoire. Peripheral blood mononuclear cells from six pairs of healthy monozygotic twins, six pairs of monozygotic twins discordant for RA, and nine siblings of a large family, including three RA patients, were examined for their TCRB gene repertoires. Among healthy twins and siblings, the BV repertoires between HLA-identical pairs were significantly more similar than those of HLA-nonidentical pairs. When RA-affected members were included, the repertoires of the HLA-identical pairs discordant for RA were dissimilar compared with those of healthy pairs. TCRBV-BJ combination repertoire analysis of CD4 and CD8 T cell subsets from the twins showed that the dissimilarity was primarily confined to CD8 T cells in the healthy identical twins, whereas it was seen in both CD4 and CD8 T cell subsets in the RA-discordant twins. These results suggest (i) the presence of RA modifies the genetically controlled TCR repertoire of peripheral T cells, and (ii) the RA-associated alterations appear to occur more frequently in CD4 T cells than in CD8 T cells.

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“…Finally, when identical twins discordant for RA were studied, their BV BJ repertoires appeared almost identical [8]. However, statistical analysis demonstrated that they were slightly different [9]. Similar results were obtained by Walser-Kuntz et al when comparing the repertoires of HLA-DR matched RA patients and controls [7].…”

T cell receptor beta chain (TCR-Vβ) repertoire of circulating CD4+CD25−, CD4+CD25lowand CD4+CD25highT cells in patients with long-term renal allograft survival

“…The increased percentage of particular Vβ families in ChrRx and LTS patients could reflect a selective expansion of alloreactive and Treg cells as a consequence of persistent exposure to donor alloantigens. Other reports have demonstrated that age [44], autoimmune diseases [45,46] and viral infections [47,48] could also influence the TCR repertoire. We can not be sure whether these factors influenced our results; however, our healthy controls were matched by age with LTS patients and none of them have clinical autoimmune diseases.…”

Formation of peripheral immunoreceptor repertoire for antigens: Potential relationship to the pathogenesis of rheumatoid arthritis

“…Turbulence of the genetically regulated alp T cell repertoire is inostly attributable to clonal expansions of CD8 cells and, to a lesser extent, those of CD4 cells (49,50). Moreover, a single TCR can potentially interact with several different peptide-MHC complexes.…”