Abstract
The influence of the environment and of the major histocompatibility complex (MHC) in shaping the human T-cell receptor β-chain variable region (TCRBV) repertoire has not been systematically studied. Here, expression of TCRBV gene families was estimated by a sensitive polymerase chain reaction (PCR)-based method. Serial studies of peripheral blood, performed at 2-week intervals over a 3-month period, revealed that fluctuation in the expression of many TCRBV genes occurred in healthy individuals and in the absence of clinically evident infections. Fluctuation of TCRBV4, TCRBV5.2, TCRBV9, and TCRBV13.1 genes were present in all subjects. Additional TCRBV genes fluctuated in some but not in other individuals. Comparison of the TCRBV repertoire between these unrelated individuals indicated differences in the mean expression of TCRBV5.1, TCRBV9, TCRBV11, TCRBV15, TCRBV17, and TCRBV20 genes. For any TCRBV gene, intersubject differences were generally of a magnitude of twofold or less. Larger differences characterized the TCRBV repertoire of CD4 compared to CD8 cells. Some differences, for example over-representation of TCRBV2 and TCRBV5.1 on CD4, and TCRBV10, TCRBV14, and TCRBV16 on CD8 cells, were present in most subjects. Individuals homozygous for DR2- or DR3-bearing extended MHC haplotypes displayed similar individual variability of TCRBV expression. These data indicate that the circulating TCRBV repertoire in humans is both dynamic and diverse. Both environment and MHC effects contribute to the diversity of TCRBV expression.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Baccala R., Kono D. H., Walker S., Baldears R. S., and Theofilopoulos A. N. Genomically imposed and somatically modified human thymocyte Vβ. Proc Natl Acad Sci USA 88: 2908–2912, 1991
Bill J., Appel V. B., and Palmer E. An analysis of T-cell receptor variable region gene expression in major histocompatibility complex disparate mice. Proc Natl Acad Sci USA 85: 9184–9188, 1988
Chelly J., Kaplan J., Maire P., Gautron S., and Kahn A. Transcription of the dystrophin gene in human muscle and non-muscle tissues. Nature 333: 958–960, 1988
Choi Y., Kotzin B., Herron L., Callahal J., Marrack P., and Kappler J. Interaction of Staphylococcus aureus toxin “superantigens” with human T cells. Proc Natl Acad Sci USA 86: 8941–8945, 1989
Cossarizza A., Kahan M., Ortolani C., Franceschi C., and Londei M. Preferential expression of Vβ6.7 domain on human peripheral CD4+ T cells. Implification for positive selection of T cells in man. Eur J Immunol 21: 1571–1574, 1991
Davis M. M. and Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature 334: 395–402, 1988
DerSimonian H., Band H., and Brenner M. B. Increased frequency of T cell receptor Vα paticipates in shaping the peripheral T-cell repertoire. J Exp Med 174: 639–648, 1991
Gillant A. R. and Goebel J. J. Nonlinear regression with autoaggressive errors. J Am Statist Assn 71: 961–967, 1976
Grunewald J., Jandon C. H., and Wigzell H. Biased expression of individual T cell receptor gene segments in CD4+ and CD8+ human peripheral blood T lymphocytes. Eur J Immunol 21: 819–822, 1991
Gulwani-Akolkar B., Posnet D. N., Janson C. H., Grunewald J., Wigzell H., Akolkar P., Gregerson P. K., and Silver J. T cell receptor V-segment frequencies in peripheral blood T cells correlate with human leukocyte antigen type. J Exp Med 174: 1139–1146, 1991
Herman A., Kappler J. W., Marrack P., and Pullen A. M. Superantigens: Mechanism of T-cell stimulation and role in immune responses. Annu Rev Immunol 9: 745–772, 1991
Howell M. D., Diveley J. P., Lundeen K. A., Esty A., Winters S. T., Carlo D. J., and Brostoff S. W. Limited T-cell receptor β-chain heterogeneity among interleukin 2 receptor-positive synovial T cells suggests a role for superantigen in rheumatoid arthritis. Proc Natl Acad Sci USA 88: 10921–10925, 1991
Imberti L., Sottini A., Spagnoli G., and Primi D. Expression of the human Vβ8 gene product preferentially correlates with class II major histocompatibility complex restriction specificity. Eur J immunol 20: 2817–2819, 1990
Loveridge J. A., Rosenberg W. M. C., Kirkwood T. B. L., and Bell J. I. The genetic contribution to human T-cell receptor repertoire. Immunology 74: 246–250, 1991
Malhotra U., Spielman R., and Concannon P. Variability in T cell receptor Vβ gene usage in human peripheral blood lymphocytes. J Immunol 149: 1802–1808, 1992
Marrack P. and Kappler J. W. The staphylococcal enterotoxins and their relatives. Science 248: 705–711, 1990
Miller R. G. Jr. Simultaneous Statistical Inference, Springer, New York Berlin Heidelberg, 1981
Moller D. R., Konishi K., Kirby M., Balbi B., and Crystal R. G. Bias toward use of a specific T cell receptor β-chain variable region in a subgroup of individuals with sarcodosis. J Clin Invest 82: 1183–1191, 1988
Moss P. A. H., Rosenberg W. M. C., and Bell J. I. The human T cell receptor in health and disease. Annu Rev Immunol 10: 71–96, 1992
Ramakrishnan N. S., Grunewald J., Janson C. H., and Wigzell H. Nearly identical T-cell receptor V-gene usage at birth in two cohorts of distinctly different ethnic origin: influence of environment in the final maturation in the adult. Scand J Immunol 36: 71–78, 1992
Rocha B. and von Bohmer H. Peripheral selection of the T cell repertoire. Science 251: 1225–1228, 1991
Rosenberg W. M. C., Moss A. H., and Bell J. I. Variation in human T cell repertoire Vβ and Jβ repertoire: analysis using anchor polymerase chain reaction. Eur J Immunol 22: 541–549, 1992
Seboun E., Robinson M. A., Kindt T. J., and Hauser S. L. Insertion/deletion-related polymorphisms in the human T cell receptor β gene complex. J Exp Med 170: 1263–1267, 1989
Singer P. A., Balderas R. S., and Theofilopoulos A. N. Thymic selection defines multiple T cell receptor Vβ ‘repertoire phenotypes’ at the CD4/CD8 subset level. EMBO J 9: 3641–3648, 1990
Tomai M. A., Aelion J. A., Dockter M. E., Majumdar G., Spinella D. G., and Kotb M. T cell receptor V gene usage by human T cells stimulated with the superantigen streptococcal M protein. J Exp Med 174: 185–188, 1991
Wucherpfennig K. W., Ota K., Endo N., Swidman J. G., Rosenzweig A., Weiner H. L., and Hafler D. A. Shared human T cell receptor Vβ usage to immunodominant regions of myelin basic protein. Science 248: 1016–1018, 1990
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Usuku, K., Joshi, N., Hatem, C.J. et al. The human T-cell receptor β-chain repertoire: longitudinal fluctuations and assessment in MHC matched populations. Immunogenetics 38, 193–198 (1993). https://doi.org/10.1007/BF00211519
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00211519