Abstract
Sensitivity to house dust mite antigens in atopic individuals is a major cause of allergic diseases, ranging from asthma to rhinitis and dermatitis. We have studied the T-cell receptor (TCR) usage of house-dust-mite-specific CD4+ T-cell clones isolated from an atopic individual, by using the anchored polymerase chain reaction, and have analyzed the peripheral TCR repertoire of the same individual. Several T-cell clones had identified TCRs at the sequence level, despite the fact that they had been independently isolated, in some cases, in different years. These data suggest the presence in vivo of long-lived T-cell clones. We have also shown that junctional sequences identical to these clones are present in peripheral blood T cells taken 6 years after the isolation of the T-cell clones. The analysis of TCR genes used by the panel of clones reveals oligoclonality, with the variable (V) region gene segments V alpha 8 and V beta 3 being dominant, although there is minimal conservation of junctional sequences. The results have implications for understanding the TCR recognition of an environmental aeroallergen and the life span of T-cell clones in vivo during a chronic immune response.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Acha-Orbea H., Mitchell D. J., Timmermann L., Wraith D. C., Tausch G. S., Waldor M. K., Zamvil S. S., McDevitt H. O., Steinman L. Limited heterogeneity of T cell receptors from lymphocytes mediating autoimmune encephalomyelitis allows specific immune intervention. Cell. 1988 Jul 15;54(2):263–273. doi: 10.1016/0092-8674(88)90558-2. [DOI] [PubMed] [Google Scholar]
- Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- Davies T. F., Martin A., Concepcion E. S., Graves P., Cohen L., Ben-Nun A. Evidence of limited variability of antigen receptors on intrathyroidal T cells in autoimmune thyroid disease. N Engl J Med. 1991 Jul 25;325(4):238–244. doi: 10.1056/NEJM199107253250404. [DOI] [PubMed] [Google Scholar]
- 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]
- Ferradini L., Roman-Roman S., Azocar J., Michalaki H., Triebel F., Hercend T. Studies on the human T cell receptor alpha/beta variable region genes. II. Identification of four additional V beta subfamilies. Eur J Immunol. 1991 Apr;21(4):935–942. doi: 10.1002/eji.1830210412. [DOI] [PubMed] [Google Scholar]
- Hansen T., Qvigstad E., Lundin K. E., Thorsby E. Sequences of four previously undescribed human T-cell receptor beta chain variable genes. Tissue Antigens. 1991 Sep;38(3):99–103. doi: 10.1111/j.1399-0039.1991.tb02020.x. [DOI] [PubMed] [Google Scholar]
- Hedrick S. M., Engel I., McElligott D. L., Fink P. J., Hsu M. L., Hansburg D., Matis L. A. Selection of amino acid sequences in the beta chain of the T cell antigen receptor. Science. 1988 Mar 25;239(4847):1541–1544. doi: 10.1126/science.2832942. [DOI] [PubMed] [Google Scholar]
- Ishizaka K. Regulation of IgE synthesis. Annu Rev Immunol. 1984;2:159–182. doi: 10.1146/annurev.iy.02.040184.001111. [DOI] [PubMed] [Google Scholar]
- Kimura N., Toyonaga B., Yoshikai Y., Du R. P., Mak T. W. Sequences and repertoire of the human T cell receptor alpha and beta chain variable region genes in thymocytes. Eur J Immunol. 1987 Mar;17(3):375–383. doi: 10.1002/eji.1830170312. [DOI] [PubMed] [Google Scholar]
- Klein M. H., Concannon P., Everett M., Kim L. D., Hunkapiller T., Hood L. Diversity and structure of human T-cell receptor alpha-chain variable region genes. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6884–6888. doi: 10.1073/pnas.84.19.6884. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lehmann P. V., Forsthuber T., Miller A., Sercarz E. E. Spreading of T-cell autoimmunity to cryptic determinants of an autoantigen. Nature. 1992 Jul 9;358(6382):155–157. doi: 10.1038/358155a0. [DOI] [PubMed] [Google Scholar]
- Li Y., Szabo P., Robinson M. A., Dong B., Posnett D. N. Allelic variations in the human T cell receptor V beta 6.7 gene products. J Exp Med. 1990 Jan 1;171(1):221–230. doi: 10.1084/jem.171.1.221. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Michie C. A., McLean A., Alcock C., Beverley P. C. Lifespan of human lymphocyte subsets defined by CD45 isoforms. Nature. 1992 Nov 19;360(6401):264–265. doi: 10.1038/360264a0. [DOI] [PubMed] [Google Scholar]
- Miossec C., Caignard A., Ferradini L., Roman-Roman S., Faure F., Michalaki H., Triebel F., Hercend T. Molecular characterization of human T cell receptor alpha chains including a V delta 1-encoded variable segment. Eur J Immunol. 1991 Apr;21(4):1061–1064. doi: 10.1002/eji.1830210430. [DOI] [PubMed] [Google Scholar]
- Moss P. A., Moots R. J., Rosenberg W. M., Rowland-Jones S. J., Bodmer H. C., McMichael A. J., Bell J. I. Extensive conservation of alpha and beta chains of the human T-cell antigen receptor recognizing HLA-A2 and influenza A matrix peptide. Proc Natl Acad Sci U S A. 1991 Oct 15;88(20):8987–8990. doi: 10.1073/pnas.88.20.8987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moss P. A., Rosenberg W. M., Zintzaras E., Bell J. I. Characterization of the human T cell receptor alpha-chain repertoire and demonstration of a genetic influence on V alpha usage. Eur J Immunol. 1993 May;23(5):1153–1159. doi: 10.1002/eji.1830230526. [DOI] [PubMed] [Google Scholar]
- O'Hehir R. E., Bal V., Quint D., Moqbel R., Kay A. B., Zanders E. D., Lamb J. R. An in vitro model of allergen-dependent IgE synthesis by human B lymphocytes: comparison of the response of an atopic and a non-atopic individual to Dermatophagoides spp. (house dust mite). Immunology. 1989 Apr;66(4):499–504. [PMC free article] [PubMed] [Google Scholar]
- O'Hehir R. E., Mach B., Berte C., Greenlaw R., Tiercy J. M., Bal V., Lechler R. I., Trowsdale J., Lamb J. R. Direct evidence for a functional role of HLA-DRB1 and -DRB3 gene products in the recognition of Dermatophagoides spp. (house dust mite) by helper T lymphocytes. Int Immunol. 1990;2(9):885–892. doi: 10.1093/intimm/2.9.885. [DOI] [PubMed] [Google Scholar]
- O'Hehir R. E., Young D. B., Kay A. B., Lamb J. R. Cloned human T lymphocytes reactive with Dermatophagoides farinae (house dust mite): a comparison of T- and B-cell antigen recognition. Immunology. 1987 Dec;62(4):635–640. [PMC free article] [PubMed] [Google Scholar]
- Okumura K., Tada T. Regulation of homocytotropic antibody formation in the rat. 3. Effect of thymectomy and splenectomy. J Immunol. 1971 Apr;106(4):1019–1025. [PubMed] [Google Scholar]
- Rawle F. C., Mitchell E. B., Platts-Mills T. A. T cell responses to the major allergen from the house dust mite Dermatophagoides pteronyssinus, Antigen P1: comparison of patients with asthma, atopic dermatitis, and perennial rhinitis. J Immunol. 1984 Jul;133(1):195–201. [PubMed] [Google Scholar]
- Roman-Roman S., Ferradini L., Azocar J., Genevée C., Hercend T., Triebel F. Studies on the human T cell receptor alpha/beta variable region genes. I. Identification of 7 additional V alpha subfamilies and 14 J alpha gene segments. Eur J Immunol. 1991 Apr;21(4):927–933. doi: 10.1002/eji.1830210411. [DOI] [PubMed] [Google Scholar]
- Rosenberg W. M., Moss P. A., Bell J. I. Variation in human T cell receptor V beta and J beta repertoire: analysis using anchor polymerase chain reaction. Eur J Immunol. 1992 Feb;22(2):541–549. doi: 10.1002/eji.1830220237. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sottini A., Imberti L., Fiordalisi G., Primi D. Use of variable human V delta genes to create functional T cell receptor alpha chain transcripts. Eur J Immunol. 1991 Oct;21(10):2455–2459. doi: 10.1002/eji.1830211023. [DOI] [PubMed] [Google Scholar]
- Sottini A., Imberti L., Gorla R., Cattaneo R., Primi D. Restricted expression of T cell receptor V beta but not V alpha genes in rheumatoid arthritis. Eur J Immunol. 1991 Feb;21(2):461–466. doi: 10.1002/eji.1830210231. [DOI] [PubMed] [Google Scholar]
- Stewart G. A., Ward L. D., Simpson R. J., Thompson P. J. The group III allergen from the house dust mite Dermatophagoides pteronyssinus is a trypsin-like enzyme. Immunology. 1992 Jan;75(1):29–35. [PMC free article] [PubMed] [Google Scholar]
- Takihara Y., Reimann J., Michalopoulos E., Ciccone E., Moretta L., Mak T. W. Diversity and structure of human T cell receptor delta chain genes in peripheral blood gamma/delta-bearing T lymphocytes. J Exp Med. 1989 Feb 1;169(2):393–405. doi: 10.1084/jem.169.2.393. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Toyonaga B., Yoshikai Y., Vadasz V., Chin B., Mak T. W. Organization and sequences of the diversity, joining, and constant region genes of the human T-cell receptor beta chain. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8624–8628. doi: 10.1073/pnas.82.24.8624. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vandenbark A. A., Hashim G., Offner H. Immunization with a synthetic T-cell receptor V-region peptide protects against experimental autoimmune encephalomyelitis. Nature. 1989 Oct 12;341(6242):541–544. doi: 10.1038/341541a0. [DOI] [PubMed] [Google Scholar]
- Wierenga E. A., Snoek M., Jansen H. M., Bos J. D., van Lier R. A., Kapsenberg M. L. Human atopen-specific types 1 and 2 T helper cell clones. J Immunol. 1991 Nov 1;147(9):2942–2949. [PubMed] [Google Scholar]
- Wilson R. K., Lai E., Concannon P., Barth R. K., Hood L. E. Structure, organization and polymorphism of murine and human T-cell receptor alpha and beta chain gene families. Immunol Rev. 1988 Jan;101:149–172. doi: 10.1111/j.1600-065x.1988.tb00736.x. [DOI] [PubMed] [Google Scholar]
- Wilson R. K., Lai E., Kim L. D., Hood L. Sequence and expression of a novel human T-cell receptor beta-chain variable gene segment subfamily. Immunogenetics. 1990;32(6):406–412. doi: 10.1007/BF00241634. [DOI] [PubMed] [Google Scholar]
- Wraith D. C., Smilek D. E., Mitchell D. J., Steinman L., McDevitt H. O. Antigen recognition in autoimmune encephalomyelitis and the potential for peptide-mediated immunotherapy. Cell. 1989 Oct 20;59(2):247–255. doi: 10.1016/0092-8674(89)90287-0. [DOI] [PubMed] [Google Scholar]