N. Mizushima et al., HLA-DEPENDENT PERIPHERAL T-CELL RECEPTOR (TCR) REPERTOIRE FORMATION AND ITS MODIFICATION BY RHEUMATOID-ARTHRITIS (RA), Clinical and experimental immunology, 110(3), 1997, pp. 428-433
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.