CELL-RECEPTOR REPERTOIRE DIFFERENCES BETWEEN AFRICAN-AMERICANS AND CAUCASIANS ASSOCIATED WITH POLYMORPHISM OF THE TCRBV3S1 (V-BETA-3.1) GENE

The generation of TCR diversity occurs primarily through rearrangement of germline DNA. Genetic polymorphism of the TCR chains appears to be a rarer mechanism for generating repertoire differences between races . Flow cytometric analysis of the TCR beta repertoire in a population of healthy African Americans (n = 30) and Caucasians (n = 30) revealed a significant difference in the frequency of cells bearing V beta 3.1 , but not V beta 2, V beta 5.1, V beta 5.2-5.3, V beta 6.7, V beta 8.1 -8.2, V beta 12.1, V beta 13.3, or V beta 19. African Americans had a significantly lower frequency of V beta 3.1(+) cells, in both the CD4( +) (2.55 +/- 0.36% vs 4.85 +/- 0.43%, p = 0.0001) and the CD8(+) (3.03 +/- 0.54% vs 5.32 + 0.57%, p = 0.004) population than did Caucasians, and this difference was independent of the age of the individuals. An alysis of genomic DNA revealed that the observed differences in freque ncy of V beta 3.1(+) cells correlated with a recently described polymo rphism of the recombination signal sequence of the TCRBV3S1 gene. Alle le 1, associated with a lower frequency of V beta 3.1(+) cells, was mo re commonly present in African Americans (0.68 vs 0.43), whereas allel e 2, associated with a higher frequency of V beta 3.1(+) cells, was mo re commonly present in Caucasians (0.31 vs 0.56). This study demonstra tes the potential for TCR repertoire differences, based on genetic pol ymorphism, between African Americans and Caucasians.