SUMMARYThe T ceil receptor (TCR) V/i repertoire in peripherai biood iymphocytes(PBL)ofa iargc number of iieaithy individuais was anaiysed by quantifying V/j-specific tnRNA using the method of anchored muitiprimer DNA ampiification and a reverse dot blot assay. Among 16 V/f gene families examined, partieular V/f genes were noted to be unequaiiy expressed in the PBL of 70 heaithy donors. The Irequently used genes belong to the V/M. 5. 6. 8 and i3 (i2) famJiies. whiie V/J I, 9 and i5 were the ieast frequentiy used gene famiiics. This bias in gene usage was observed in ail individuais, Mariccd deviation from the mean percentage usage was noted for some V/i genes in individuals when liieir PBL were examined serlaiiy. bul the common pattern of biased usage was not grossiy distorted. When the TCR repertoire of different ethnic groups was examined, a iower mean frequency of V/i 3,2 was seen in the repertoire of 19 Caucasians compared with 25 age-malched Samoans (/'<0003), Conversely, the expression of V/f 5.1 and of V/^ 5,3 was higher in Caucasians tiian in 5i age-malchcd Poiynesians (Maoris and Samoans, /*<0003). Considering the 20' ' >> co-eflicicnt of variation in liie estimate of \fi gene usage, our data from 70 unreiated individuals .suggest that in PBL, individuai variations in the TCR repertoire were superimposed upon a common biased usage of V/f genes in the generai popuiation. Keywords T celi receptor TCR V/i gene usage Polynesian INTRODLICTIONThe repertoire of T celi responses is derived from the rearrangement of the a, fi, y and 6 T eeii receptor (TCR) genes. The number of TCR genes, their V(D)J gene famiiies and subfamilies, as weii as the variabiiity of recombination sites provide for a large rearranged repertoire [I|, However, not aii possibie recombinations are expressed in mature T ceiis. Precursor T cells with rearranged TCR genes are positively selected during their development in the thymus if their TCR were capabie of recognizing antigen presented by seif-MHC. There is evidence that tiiose T cells which are potentially autoreactive are deleted and iaii toieave the thymus [2]. As this selection is influenced by self-MHC. individuals of different MHC hapiotypes may be expected to seicct for discordant sets of TCR gene rearrangements. The expressed T celi repertoire is aiso affected by environmentai factors such as antigens presented by MHC moiecuics lo T ceiis [3]. In addilion. superantigens in combination with MHC are known to activate and expand T ceii clones which bear particular TCR Vji chains [4]. ll is ihus not surprising that identical twins with the same TCR and MHC genes express non-identical TCR repertoires [5.6]. Diverse individuai patterns of gene usage are therefore generated and presumabiy contribute to individuai differences in immune responses or susceptibiiity to disease [7.8). As popuiaiions exposed lo the same environmentai factors but with differing MHC hapiotypes may express dissimiiar T ceil lepcrtoires. lhe selection of specific V/f genes by distinct ethnic groups could expiain i...
Objective. To analyze HLA–DR4 alleles in New Zealand Polynesians with rheumatoid arthritis (RA).Methods. Thirty Polynesians and 30 Caucasians with RA, as well as 65 Polynesian and 60 Caucasian healthy blood donors, were DR4 subtyped using the polymerase chain reaction and sequence‐specific oligonucleotide probes.Results.The frequency of DR4 (DRB1*04) was increased in both Polynesian (P <0.001) and Caucasian (P <0.005) RA patients compared with race‐matched controls. Dw4 (DRB1*0401) was detected in 15 of 30 Caucasian patients but only 2 of 30 Polynesian patients (P <0.001). In Polynesians, RA was associated with Dw15 (DRB1*0405), which was present in 11 of 30 patients and 3 of 65 controls (P < 0.001). Dw13 (DRB1*0403) was the most frequent DR4 allele in healthy Polynesians, but was not significantly associated with RA.Conclusion. The predominance of the Dw13 subtype in Polynesians may explain in part the low prevalence of RA in this population. The association of Dw15 with RA in Polynesians supports the hypothesis that the third hypervariable region of DRβ determines susceptibility to RA.
Objective. Peptides presented by DR4/1 may be involved in the pathogenesis of rheumatoid arthritis (RA). T cell responses to DR4/1‐restricted peptides unrelated to the causative antigen may be altered in RA. Thus, DR4/1‐restricted lymphocyte responses in healthy volunteers and patients with RA were determined. Methods. Peripheral blood lymphocytes (PBL) and synovial lymphocytes were cultured with synthetic peptides spanning the 19‐kd Mycobacterium tuberculosis (MT) protein. Results. 3H‐thymidine uptake by PBL from 5 of 7 healthy individuals and 5 of 7 RA patients increased in response to the N‐terminal peptide (residues 1–20). Eleven fresh synovial fluid and 4 fresh synovial tissue (ST) lymphocyte samples did not proliferate in response to any of the peptides. However, the same T cell epitope was identified by ST lymphocytes when these were precultured. The N‐terminal peptide was not a common antibody‐binding site, unlike several of the other peptides. Conclusion. Similar responses by RA and normal PBL to a DR4/1‐restricted immunodominant T cell epitope on the 19‐kd MT protein were observed. The responses were more readily detected in PBL than in synovial lymphocytes. These observations may be relevant for assessing unrelated synthetic peptides in the development of DR4/1‐restricted peptide immunotherapy.
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