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Differential usage of T cell receptor V gene segments in CD4+ and CD8+ subsets of T lymphocytes in monozygotic twins
Abstract
The TCR confers immunity by the specific recognition of foreign Ag peptides in the context of self-MHC molecules. The mechanisms controlling TCR selection and repertoire generation are not clearly understood and seem to occur in an apparently random, (self) Ag-driven manner. To address the question to what extent the TCR repertoire is randomly shaped or genetically predetermined, we have analyzed the alpha beta TCR repertoire of the CD4+ and CD8+ subsets of peripheral blood lymphocyte cultures of monozygotic twins by using the polymerase chain reaction technique with TCR V region gene family-specific oligonucleotide primers. Our studies demonstrate that there is high concordance in the overall patterns of V gene usage within a pair of twins, particularly in V beta usage (mean V beta CD4+ R2 = 0.869 and CD8+ R2 = 0.833) and to a lesser extent V alpha usage (mean V alpha CD4+ R2 = 0.621 and CD8+ R2 = 0.627); whereas the patterns between unrelated individuals show more variability. This study has also demonstrated that the V alpha and V beta genes are not randomly used within the CD4+ and CD8+ subsets. We observed significant preferential skewing of several V alpha or V beta gene families to either the CD4+ or CD8+ subset in the majority of individuals analyzed (p-value range = 0.0476 to < 0.001). In particular, V alpha 11, 17, 22, and V beta 3, 9, 12, 18 were skewed to the CD4+ subset; whereas V alpha 2, 6, 12, 15, 20 and V beta 7, 14, 17 were skewed to the CD8+ subset. Furthermore, a number of the V genes showed patterns of skewing consistent only within a pair of twins. In three pairs of twins, V beta 2 was skewed to the CD4+ subset, whereas the fourth pair used almost equal frequencies of V beta 2 in both subsets. This observation was made for the V beta 2, 4, 5, 6, 8, 19 and V alpha 7, 16, 18, 21 families. Finally, the ratio of the relative V gene usage frequency that could be observed within an individual was conserved within the sets of twins; for instance, the relative amount of V beta 2 to that of V beta 3 was higher in both individuals of one set of twins, whereas it was lower in all of the other three sets. Together these observations suggest that the predominant influence shaping the TCR repertoire is genetically predetermined, of which, HLA-predicted selection mechanisms exerted during thymic maturation might be contributing factors.
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“Given the great complexity of the T- and B-cell repertoires and a large stochastic element in choosing which cells will respond to a given stimulus, and somatic mutations in B cells, the precise composition will differ in each individual, even in monozygotic twins [66].”
From Evolution of the immune system in humans from infancy to old age (2015) · cites this paper as [66]
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“Recently, studies of monozygotic twin pairs have shown that they have a greater similarity in their TCRAVand TCRB-V gene usage than other sibs or unrelated individuals (Malhotra et al. 1992; Moss et al. 1993; Hawes et al. 1993; Loveridge et al. 1991), but the number of such pairs is small (one, one, four, and five res…”
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McCoy, J. P. (1998) · Clinical Immunology Newsletter · doi:10.1016/s0197-1859(00)89170-0
Hawes, G. E., Struyk, L., Godthelp, B. C., et al. (1995) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1995.tb44530.x
Self-citationThe Circulating Human Peripheral T-Cell Repertoire
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Metadata
- Authors
- Hawes, G. E., Struyk, L., & van den Elsen, P. J.
- Affiliations
- Leiden University Medical Center (NL)
- Department of Immunohematology, University Hospital Leiden ,
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 1993-03-01
- Volume
- 150
- Issue
- 5
- Pages
- 2033-2045
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1594245074
- Cited by
- 119
- References
- 0
- Citations by year
- 2021: 1 · 2019: 2 · 2017: 1 · 2015: 2 · 2014: 1 · 2012: 1
- FWCI
- 9.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- T cell receptor V gene usage, T cell receptor repertoire, CD4+ T cells, CD8+ T cells, monozygotic twins, V beta gene usage
- MeSH terms
- Adult, Base Sequence, Female, Fluorescent Antibody Technique, Gene Frequency, Humans, Molecular Sequence Data, Twins, Monozygotic, CD4 Antigens, T-Lymphocyte Subsets, Receptors, Antigen, T-Cell, alpha-beta, CD8 Antigens
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