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Microsatellite polymorphisms of nine Eurasian populations (> 1200 chromosomes) were analyzed for the following loci: i) intronic (gt)n stretches of three T cell receptor (TCR) B loci on chromosome 7 (TCRBV6S1, TCRBV6S3, TCRBV6S7); ii) an intergenic (gt)n repeat in the region between the TCRDV3 and TCRAJ61 elements on chromosome 14; iii) two tetranucleotide simple repeats (D12S66, D12S67), not linked to known genes on chromosome 12; iv) a Y-chromosomal (gata)n polymorphism (DYS19). In general, allele frequencies and heterozygosity rates were similar, but specific alleles were missing in one or more populations. Distinct DYS19 alleles predominated in particular cohorts. Different allele frequencies were observed for the TCR loci in European and Asian populations. Tetranucleotide polymorphisms were distributed normally, whereas TCR alleles displayed bimodal frequency profiles. For TCRBV6S1 and TCRBV6S7, this profile reflects a diallelic protein polymorphism that correlates exactly with the length of the intronic repeats.

In a panel of wild mice trapped in different geographical regions, the concomitant expression of V beta 17 T cell receptors and I-E histocompatibility molecules is frequent. By Southern blot analysis, eight forms of V beta 17 genes have been distinguished that encode five kinds of V beta 17 domains. Populations of Asia display the highest level of polymorphism and include all the V beta 17 forms and domains. The V beta 17 T cells of wild origin are deleted in mice expressing Mls-3 and related superantigens. Wild mice use V beta 17 domains different than the one of laboratory strains. Together with endogenous superantigens polymorphism, this accounts for the observed low frequency of clonal deletion cases in natural populations.

We have previously analysed the T-cell receptor (TCR) V-gene usage in peripheral blood T lymphocytes from a group of healthy Scandinavians, and described a biased representation (i.e. a statistically significant higher median representation) for some of the TCR V genes towards the CD4+ subpopulation. In a subsequent study the usage of the same V genes was analysed in single positive (CD4+ CD8- and CD4- CD8+) human thymocytes, and a similar type of skewness was noted. These observations might be explained by an influence of the specificity of the TCR of thymocytes on the maturation into the CD4+ or the CD8+ lineage. Such a model would assume an interaction between a common determinant on the major histocompatibility complex (MHC) class I or class II molecules, or with a peptide that is preferentially presented by either of the two molecules, and the TCR on the maturing thymocyte. To investigate the possible influence of a different genetic background and environment on skewed TCR V-gene representation, we have in this study analysed the TCR V-gene usage in peripheral blood and umbilical cord blood lymphocytes obtained from Asians, with a different ethnic and environmental background from our previous Scandinavian subjects. In the umbilical cord blood lymphocytes the TCR V-gene usage was close to identical between the two different ethnic groups in both CD4+ and CD8+ subpopulations. Analysing the peripheral blood lymphocyte (PBL) TCR V-gene usage, we found that three of the four monoclonal antibodies (MoAb) with a biased reactivity towards the CD4+ subpopulation in the Scandinavian group also showed a similar skewed reactivity in this study. Thus, the majority of the TCR V genes were used in a similar way. Some minor but definite discrepancies could be detected when comparing TCR V-gene usage in adult individuals from these two different ethnic groups. These differences could be inferred to be due to selective peripheral expansion through environmental pressure of T cells utilizing a specific V beta gene segment. We conclude that a striking preservation of biased TCR V-gene usage does exist in humans of distinctly different ethnic origin.