Population study of T cell receptor Vβ gene usage in peripheral blood lymphocytes: differences in ethnic groups

Abstract

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...

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