Systematic study of human αβ T cell receptor V segments shows allelic variations resulting in a large number of distinct T cell receptor haplotypes

Abstract

The variation of the alpha beta T cell receptor (TCR) results mainly from rearrangements of germ-line V, D and J elements combined with the processes of N- and P-region addition. In addition to this extensive diversity, diallelic polymorphism is also recognized in V regions of beta loci. Four such polymorphisms have previously been defined, but the full extent of such variation has not yet been established. To investigate allelic polymorphism, we used a strategy based V locus-specific polymerase chain reaction and single-strand conformation polymorphisms. Studying the two V beta 2 loci and the V alpha 8.1 locus, we found that all exhibited a coding polymorphism. One of the V beta 2 loci proved to be the first multiallele segment to be recognized, with three common variants. The second V beta 2 locus, for which none of the two alleles has been identified in cDNA, appeared in fact to be a V beta orphon, in abnormal location on the chromosome 9. A yeast artificial chromosome containing part of the TCRB locus allowed us to place the first V beta 2 segment on the known map to define haplotypes with two other polymorphic segments: V beta 1 and V beta 6.7. Multiple distinct haplotypes result from combinations between these polymorphic loci, showing that V beta regions are highly variable between individuals. Two alleles exist at the V alpha 8.1 segment and both are expressed. This represents the first example of a frequent coding polymorphism for TCRA gene. The distribution of allele frequencies for these segments suggest the action of balancing selection. These data add a further dimension to TCR polymorphism and suggest new candidates to explore TCR-encoded susceptibility to autoimmune diseases.

Allergy to <i>Dermatophagoides</i> in a Group of Spanish Gypsies: Genetic Restrictions

“…The genomic DNA of all individuals was genotyped for seven polymorphisms: DRB1* and DQB1* HLA class II loci, the biallelic Ava II polymoprhism within TCR Vα8.1 [16], two polymorphisms within the FcεR1-β gene (biallelic Rsa I polymorphism in intron 2 [17]and biallelic polymorphism in the UTR [18]of exon 7), the tumor necrosis factor-β polymorphism, analyzing the biallelic Nco I polymorphism in the first intron of LTα [19]and the promoter region of the CD14 gene analyzing the biallelic Ava II polymorphism [13]. …”

“…Typing of the TCR Vα8.1 was performed as described by Cornelis et al [16], with minor modification [20]. Resultant products of PCR, after digestion with Ava II (New England Biolabs), were analyzed on 2% agarose gels and three genotypes were identified: 1,1 homozygote (124 and 145 bp), 1,2 heterozygote (269, 145 and 124 bp) and 2,2 homozygote (269 bp).…”

Bimodal distribution of Vβ2+CD4+ T cells in human peripheral blood

“…TCR haplotypes were established by typing the family members for six coding region TCRBV gene polymorphisms. The polymorphic TCRBV segments TCRBV1 [25], BV2S1 [26], BV6S7 [27], BV12S2 [28] and BV18 [29] were typed as previously described. TCRBV6S1 polymorphisms (Reyburn et al, in preparation) were allotyped by singlestrand conformational polymorphism (SSCP) of a PCR product generated using the primers 5'-TCCTGTTCTCA-ACTTGTGTCTCCG-3' and 5'-GTTTATGAGCAGGA-AGGAGGCGAT-3'.…”

Genetics of Asthma

“…Several Va genes have been recognized to be polymorphic [53] and limitation of the response to an allergen may correspond to these polymorphisms. Particular TCR -Va usage may induce IL-4-dominant helper T cells (Th2), which enhance IgE production [54].…”