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. 1995 Sep;1(6):614–624.

Oligoclonality in the human CD8+ T cell repertoire in normal subjects and monozygotic twins: implications for studies of infectious and autoimmune diseases.

J Monteiro 1, R Hingorani 1, I H Choi 1, J Silver 1, R Pergolizzi 1, P K Gregersen 1
PMCID: PMC2229970  PMID: 8529128

Abstract

BACKGROUND: We have previously demonstrated CD8+ T cell clonal dominance using a PCR assay for the CDR3 length of T cell receptors belonging to a limited number of TCRBV segments/families. In this study, we have modified this approach in order to analyze more comprehensively the frequency of oligoclonality in the CD8+ T cell subset in 25 known TCRBV segments/families. In order to assess the relative roles of genes and environment in the shaping of a clonally restricted CD8+ T cell repertoire, we have analyzed clonal dominance in the CD8+ T cell population of monozygotic twins, related siblings, and adoptees. MATERIALS AND METHODS: Oligoclonality was assessed in the CD8+ T cell subsets using a multiplex PCR approach to assay for CDR3 length variation across 25 different TCRBV segments/families. Specific criteria for oligoclonality were established, and confirmed by direct sequence analysis of the PCR products. This assay was used to investigate the CD8+ T cell repertoire of 56 normal subjects, as well as six sets of monozygotic (MZ) twins. RESULTS: Seventy-two percent of normal subjects (n = 56) had evidence of oligoclonality in the CD8+ T cell subset, using well-defined criteria. Although MZ twins frequently displayed CD8+ T cell clonal dominance, the overall pattern of oligoclonality was very diverse within each twin pair. However, we occasionally observed dominant CD8+ T cell clones that were highly similar in sequence in both members of some twin pairs. Not a single example of such similarity was observed in normal controls or siblings. CONCLUSIONS: Oligoclonality of circulating CD8+ T cells is a characteristic feature of the human immune system; both host genetic factors and environment shape the pattern of oligoclonality in this T cell subset. The high frequency of this phenomenon in normal subjects provides a background with which to evaluate CD8+ T cell oligoclonality in the setting of infection or autoimmune disease. Further phenotypic and functional characterization of these clonally expanded T cells should provide insight into normal immune homeostasis.

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Selected References

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  1. Candéias S., Waltzinger C., Benoist C., Mathis D. The V beta 17+ T cell repertoire: skewed J beta usage after thymic selection; dissimilar CDR3s in CD4+ versus CD8+ cells. J Exp Med. 1991 Nov 1;174(5):989–1000. doi: 10.1084/jem.174.5.989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Casanova J. L., Cerottini J. C., Matthes M., Necker A., Gournier H., Barra C., Widmann C., MacDonald H. R., Lemonnier F., Malissen B. H-2-restricted cytolytic T lymphocytes specific for HLA display T cell receptors of limited diversity. J Exp Med. 1992 Aug 1;176(2):439–447. doi: 10.1084/jem.176.2.439. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Davis M. M., Bjorkman P. J. T-cell antigen receptor genes and T-cell recognition. Nature. 1988 Aug 4;334(6181):395–402. doi: 10.1038/334395a0. [DOI] [PubMed] [Google Scholar]
  4. Deapen D., Escalante A., Weinrib L., Horwitz D., Bachman B., Roy-Burman P., Walker A., Mack T. M. A revised estimate of twin concordance in systemic lupus erythematosus. Arthritis Rheum. 1992 Mar;35(3):311–318. doi: 10.1002/art.1780350310. [DOI] [PubMed] [Google Scholar]
  5. DerSimonian H., Sugita M., Glass D. N., Maier A. L., Weinblatt M. E., Rème T., Brenner M. B. Clonal V alpha 12.1+ T cell expansions in the peripheral blood of rheumatoid arthritis patients. J Exp Med. 1993 Jun 1;177(6):1623–1631. doi: 10.1084/jem.177.6.1623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fitzgerald J. E., Ricalton N. S., Meyer A. C., West S. G., Kaplan H., Behrendt C., Kotzin B. L. Analysis of clonal CD8+ T cell expansions in normal individuals and patients with rheumatoid arthritis. J Immunol. 1995 Apr 1;154(7):3538–3547. [PubMed] [Google Scholar]
  7. Gorski J., Yassai M., Zhu X., Kissela B., Kissella B [corrected to Kissela B. ]., Keever C., Flomenberg N. Circulating T cell repertoire complexity in normal individuals and bone marrow recipients analyzed by CDR3 size spectratyping. Correlation with immune status. J Immunol. 1994 May 15;152(10):5109–5119. [PubMed] [Google Scholar]
  8. Grunewald J., Jeddi-Tehrani M., Dersimonian H., Andersson R., Wigzell H. A persistent T cell expansion in the peripheral blood of a normal adult male: a new clinical entity? Clin Exp Immunol. 1992 Aug;89(2):279–284. doi: 10.1111/j.1365-2249.1992.tb06945.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hingorani R., Choi I. H., Akolkar P., Gulwani-Akolkar B., Pergolizzi R., Silver J., Gregersen P. K. Clonal predominance of T cell receptors within the CD8+ CD45RO+ subset in normal human subjects. J Immunol. 1993 Nov 15;151(10):5762–5769. [PubMed] [Google Scholar]
  10. Jorgensen J. L., Reay P. A., Ehrich E. W., Davis M. M. Molecular components of T-cell recognition. Annu Rev Immunol. 1992;10:835–873. doi: 10.1146/annurev.iy.10.040192.004155. [DOI] [PubMed] [Google Scholar]
  11. Morley J. K., Batliwalla F. M., Hingorani R., Gregersen P. K. Oligoclonal CD8+ T cells are preferentially expanded in the CD57+ subset. J Immunol. 1995 Jun 1;154(11):6182–6190. [PubMed] [Google Scholar]
  12. Oksenberg J. R., Panzara M. A., Begovich A. B., Mitchell D., Erlich H. A., Murray R. S., Shimonkevitz R., Sherritt M., Rothbard J., Bernard C. C. Selection for T-cell receptor V beta-D beta-J beta gene rearrangements with specificity for a myelin basic protein peptide in brain lesions of multiple sclerosis. Nature. 1993 Mar 4;362(6415):68–70. doi: 10.1038/362068a0. [DOI] [PubMed] [Google Scholar]
  13. Paliard X., West S. G., Lafferty J. A., Clements J. R., Kappler J. W., Marrack P., Kotzin B. L. Evidence for the effects of a superantigen in rheumatoid arthritis. Science. 1991 Jul 19;253(5017):325–329. doi: 10.1126/science.1857971. [DOI] [PubMed] [Google Scholar]
  14. Pannetier C., Cochet M., Darche S., Casrouge A., Zöller M., Kourilsky P. The sizes of the CDR3 hypervariable regions of the murine T-cell receptor beta chains vary as a function of the recombined germ-line segments. Proc Natl Acad Sci U S A. 1993 May 1;90(9):4319–4323. doi: 10.1073/pnas.90.9.4319. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Pantaleo G., Demarest J. F., Soudeyns H., Graziosi C., Denis F., Adelsberger J. W., Borrow P., Saag M. S., Shaw G. M., Sekaly R. P. Major expansion of CD8+ T cells with a predominant V beta usage during the primary immune response to HIV. Nature. 1994 Aug 11;370(6489):463–467. doi: 10.1038/370463a0. [DOI] [PubMed] [Google Scholar]
  16. Posnett D. N., Sinha R., Kabak S., Russo C. Clonal populations of T cells in normal elderly humans: the T cell equivalent to "benign monoclonal gammapathy". J Exp Med. 1994 Feb 1;179(2):609–618. doi: 10.1084/jem.179.2.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Puisieux I., Even J., Pannetier C., Jotereau F., Favrot M., Kourilsky P. Oligoclonality of tumor-infiltrating lymphocytes from human melanomas. J Immunol. 1994 Sep 15;153(6):2807–2818. [PubMed] [Google Scholar]
  18. Shanmugam A., Copie-Bergman C., Hashim G., Rebibo D., Jais J. P., Bach J. F., Bach M. A., Tournier-Lasserve E. Healthy monozygous twins do not recognize identical T cell epitopes on the myelin basic protein autoantigen. Eur J Immunol. 1994 Oct;24(10):2299–2303. doi: 10.1002/eji.1830241006. [DOI] [PubMed] [Google Scholar]
  19. Trejo V., Derom C., Vlietinck R., Ollier W., Silman A., Ebers G., Derom R., Gregersen P. K. X chromosome inactivation patterns correlate with fetal-placental anatomy in monozygotic twin pairs: implications for immune relatedness and concordance for autoimmunity. Mol Med. 1994 Nov;1(1):62–70. [PMC free article] [PubMed] [Google Scholar]
  20. Wang E. C., Taylor-Wiedeman J., Perera P., Fisher J., Borysiewicz L. K. Subsets of CD8+, CD57+ cells in normal, healthy individuals: correlations with human cytomegalovirus (HCMV) carrier status, phenotypic and functional analyses. Clin Exp Immunol. 1993 Nov;94(2):297–305. doi: 10.1111/j.1365-2249.1993.tb03447.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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