Level of Human TCRBV3S1 (V Beta 3) Expression Correlates with Allelic Polymorphism in the Spacer Region of the Recombination Signal Sequence

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 1994 May 1

PMID 8163948

Citations 21

Authors

D N Posnett

C S Vissinga

C Pambuccian

S Wei

M A Robinson

D Kostyu

P Concannon

Affiliations

Soon will be listed here.

Abstract

One of the causes of variations in the expressed human T cell receptor (TCR) BV (V beta) repertoire is genetic variation in the germline DNA. Herein evidence is provided that allelic polymorphism may affect recombination frequency for a specific V gene. Two alleles of the TCR BV3 differ only at a single nucleotide position (C/T) within the 23-bp spacer region of the recombination signal sequence. These alleles are associated with variable percentages of BV3 cells in the peripheral blood, as shown in families and in unrelated normal donors. Individuals homozygous for allele 2 have a mean of 8.1% BV3 cells, heterozygous individuals have a mean of 4.7% BV3 cells, and homozygotes for allele 1 have a mean of 1.2% BV3 cells in CD3+ CD4+ peripheral blood T cells. Since the correlation is tight in unrelated individuals and other genetic differences were not found in the vicinity of BV3, we suggest that the spacer region sequence itself modifies recombination efficiency. This allelic system provides an example of a novel mechanism by which cis-acting genetic elements may affect recombination in a natural in vivo system.

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References

Behlke M, Chou H, Huppi K, Loh D . Murine T-cell receptor mutants with deletions of beta-chain variable region genes. Proc Natl Acad Sci U S A. 1986; 83(3):767-71. PMC: 322946. DOI: 10.1073/pnas.83.3.767. View

Charmley P, Wei S, Concannon P . Polymorphisms in the Tcrb-V2 gene segments localize the Tcrb orphon genes to human chromosome 9p21. Immunogenetics. 1993; 38(4):283-6. DOI: 10.1007/BF00188805. View

Davis M, Bjorkman P . T-cell antigen receptor genes and T-cell recognition. Nature. 1988; 334(6181):395-402. DOI: 10.1038/334395a0. View

Hesse J, Lieber M, Mizuuchi K, Gellert M . V(D)J recombination: a functional definition of the joining signals. Genes Dev. 1989; 3(7):1053-61. DOI: 10.1101/gad.3.7.1053. View

Seboun E, Robinson M, Kindt T, Hauser S . Insertion/deletion-related polymorphisms in the human T cell receptor beta gene complex. J Exp Med. 1989; 170(4):1263-70. PMC: 2189474. DOI: 10.1084/jem.170.4.1263. View

Robinson M . Allelic sequence variations in the hypervariable region of a T-cell receptor beta chain: correlation with restriction fragment length polymorphism in human families and populations. Proc Natl Acad Sci U S A. 1989; 86(23):9422-6. PMC: 298508. DOI: 10.1073/pnas.86.23.9422. View

Li Y, Szabo P, Robinson M, Dong B, Posnett D . Allelic variations in the human T cell receptor V beta 6.7 gene products. J Exp Med. 1990; 171(1):221-30. PMC: 2187675. DOI: 10.1084/jem.171.1.221. View

Posnett D . Allelic variations of human TCR V gene products. Immunol Today. 1990; 11(10):368-73. DOI: 10.1016/0167-5699(90)90143-w. View

Posnett D, Janson C, Grunewald J, Wigzell H, Akolkar P, Gregersen P . T cell receptor V-segment frequencies in peripheral blood T cells correlate with human leukocyte antigen type. J Exp Med. 1991; 174(5):1139-46. PMC: 2118988. DOI: 10.1084/jem.174.5.1139. View

10.

Ramsden D, Wu G . Mouse kappa light-chain recombination signal sequences mediate recombination more frequently than do those of lambda light chain. Proc Natl Acad Sci U S A. 1991; 88(23):10721-5. PMC: 53002. DOI: 10.1073/pnas.88.23.10721. View

11.

Loveridge J, Rosenberg W, Kirkwood T, Bell J . The genetic contribution to human T-cell receptor repertoire. Immunology. 1991; 74(2):246-50. PMC: 1384600. View

12.

Davey M, Meyer M, Munkirs D, Babcock D, Braun M, Hayden J . T-cell receptor variable beta genes show differential expression in CD4 and CD8 T cells. Hum Immunol. 1991; 32(3):194-202. DOI: 10.1016/0198-8859(91)90056-f. View

13.

Hsieh C, Lieber M . CpG methylated minichromosomes become inaccessible for V(D)J recombination after undergoing replication. EMBO J. 1992; 11(1):315-25. PMC: 556452. DOI: 10.1002/j.1460-2075.1992.tb05054.x. View

14.

Maksymowych W, Gabriel C, Luyrink L, Melin-Aldana H, Elma M, Giannini E . Polymorphism in a T-cell receptor variable gene is associated with susceptibility to a juvenile rheumatoid arthritis subset. Immunogenetics. 1992; 35(4):257-62. DOI: 10.1007/BF00166831. View

15.

Schatz D, Oettinger M, Schlissel M . V(D)J recombination: molecular biology and regulation. Annu Rev Immunol. 1992; 10:359-83. DOI: 10.1146/annurev.iy.10.040192.002043. View

16.

Malhotra U, Spielman R, Concannon P . Variability in T cell receptor V beta gene usage in human peripheral blood lymphocytes. Studies of identical twins, siblings, and insulin-dependent diabetes mellitus patients. J Immunol. 1992; 149(5):1802-8. View

17.

Day C, Zhao T, Robinson M . Silent allelic variants of a T-cell receptor V beta 12 gene are present in diverse human populations. Hum Immunol. 1992; 34(3):196-202. DOI: 10.1016/0198-8859(92)90112-z. View

18.

Charmley P, Wang K, Hood L, Nickerson D . Identification and physical mapping of a polymorphic human T cell receptor V beta gene with a frequent null allele. J Exp Med. 1993; 177(1):135-43. PMC: 2190858. DOI: 10.1084/jem.177.1.135. View

19.

Hawes G, Struyk L, van den Elsen P . Differential usage of T cell receptor V gene segments in CD4+ and CD8+ subsets of T lymphocytes in monozygotic twins. J Immunol. 1993; 150(5):2033-45. View

20.

Robinson M, Mitchell M, Wei S, Day C, Zhao T, Concannon P . Organization of human T-cell receptor beta-chain genes: clusters of V beta genes are present on chromosomes 7 and 9. Proc Natl Acad Sci U S A. 1993; 90(6):2433-7. PMC: 46101. DOI: 10.1073/pnas.90.6.2433. View