HLA-DEPENDENT PERIPHERAL T-CELL RECEPTOR (TCR) REPERTOIRE FORMATION AND ITS MODIFICATION BY RHEUMATOID-ARTHRITIS (RA)

Our previous studies have disclosed that the peripheral T cell recepto r beta (TCRB) gene repertoires of RA monozygotic twins were similar. T his suggested that the TCRBV repertoire is controlled primarily by gen etic factors. Here, we examine how the combination of HLA and presence of RA influence the peripheral TCRB repertoire. Peripheral blood mono nuclear cells from six pairs of healthy monozygotic twins, six pairs o f monozygotic twins discordant for RA, and nine siblings of a large fa mily, including three RA patients, were examined for their TCRB gene r epertoires. Among healthy twins and siblings, the BV repertoires betwe en HLA-identical pairs were significantly more similar than those of H LA-nonidentical pairs. When RA-affected members were included, the rep ertoires 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 ide ntical twins, whereas it was seen in both CD4 and CD8 T cell subsets i n the RA-discordant twins. These results suggest (i) the presence of R A modifies the genetically controlled TCR repertoire of peripheral T c ells, and (ii) the RA-associated alterations appear to occur more freq uently in CD4 T cells than in CD8 T cells.