Development of Epstein-Barr virus-specific memory T cell receptor clonotypes in acute infectious mononucleosis

doi:10.1084/jem.184.5.1815

This Article

	Full Text (PDF)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JEM
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Silins, S. L.
	Articles by Misko, I. S.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Silins, S. L.
	Articles by Misko, I. S.


Social Bookmarking

	What's this?

ARTICLES

Development of Epstein-Barr virus-specific memory T cell receptor clonotypes in acute infectious mononucleosis

SL Silins, SM Cross, SL Elliott, SJ Pye, SR Burrows, JM Burrows, DJ Moss, VP Argaet and IS Misko
Epstein-Barr Virus Unit, Queensland Institute of Medical Research, The Bancroft Centre, Brisbane, Australia.

The importance of cytotoxic T lymphocytes (CTLs) in the immunosurveillance of Epstein-Barr virus (EBV)-infected B cells is firmly established, and the viral antigens of CTL recognition in latent infection are well defined. The epitopes targeted by CTLs during primary infection have not been identified, however, and there is only limited information about T cell receptor (TCR) selection. In the present report, we have monitored the development of memory TCR-beta clonotypes selected in response to natural EBV infection in a longitudinal study of an HLA-B8+ individual with acute infectious mononucleosis (IM). By stimulating peripheral blood lymphocytes with HLA-B8+ EBV-transformed B lymphoblastoid cells, the primary virus- specific CTL response was shown to include specificities for two HLA-B8- restricted antigenic determinants, FLRGRAYGL and QAKWRLQTL, which are encoded within the latent EBV nuclear antigen EBNA-3. TCR-beta sequence analysis of CTL clones specific for each epitope showed polyclonal TCR- beta repertoire selection, with structural restrictions on recognition that indicated antigen-driven selection. Furthermore, longitudinal repertoire analysis revealed long-term preservation of a multiclonal effector response throughout convalescence, with the reemergence of distinct memory T cell clonotypes sharing similar structural restrictions. Tracking the progression of specific TCR-beta clonotypes and antigen-specific TCR-V beta family gene expression in the peripheral repertoire ex vivo using semiquantitative PCR strongly suggested that selective TCR-beta expansions were present at the clonotype level, but not at the TCR-V beta family level. Overall, in this first analysis of antigen-specific TCR development in IM, a picture of polyclonal TCR stimulation is apparent. This diversity may be especially important in the establishment of an effective CTL control during acute EBV infection and in recovery from disease.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Add to Reddit Reddit Add to Technorati Technorati What's this?

This article has been cited by other articles:

Stapler, D., Lee, E. D., Selvaraj, S. A., Evans, A. G., Kean, L. S., Speck, S. H., Larsen, C. P., Gangappa, S. (2008). Expansion of Effector Memory TCR V{beta}4+CD8+ T Cells Is Associated with Latent Infection-Mediated Resistance to Transplantation Tolerance. J. Immunol. 180: 3190-3200 [Abstract] [Full Text]
Elliott, S. L., Suhrbier, A., Miles, J. J., Lawrence, G., Pye, S. J., Le, T. T., Rosenstengel, A., Nguyen, T., Allworth, A., Burrows, S. R., Cox, J., Pye, D., Moss, D. J., Bharadwaj, M. (2008). Phase I Trial of a CD8+ T-Cell Peptide Epitope-Based Vaccine for Infectious Mononucleosis. J. Virol. 82: 1448-1457 [Abstract] [Full Text]
Derre, L., Bruyninx, M., Baumgaertner, P., Devevre, E., Corthesy, P., Touvrey, C., Mahnke, Y. D., Pircher, H., Voelter, V., Romero, P., Speiser, D. E., Rufer, N. (2007). In Vivo Persistence of Codominant Human CD8+ T Cell Clonotypes Is Not Limited by Replicative Senescence or Functional Alteration. J. Immunol. 179: 2368-2379 [Abstract] [Full Text]
Schmid, J. M. P., Junge, S. A., Hossle, J. P., Schneider, E. M., Roosnek, E., Seger, R. A., Gungor, T. (2006). Transient Hemophagocytosis With Deficient Cellular Cytotoxicity, Monoclonal Immunoglobulin M Gammopathy, Increased T-Cell Numbers, and Hypomorphic NEMO Mutation. Pediatrics 117: e1049-e1056 [Abstract] [Full Text]
Miles, J. J., Silins, S. L., Brooks, A. G., Davis, J. E., Misko, I., Burrows, S. R. (2005). T-cell grit: large clonal expansions of virus-specific CD8+ T cells can dominate in the peripheral circulation for at least 18 years. Blood 106: 4412-4413 [Full Text]
Weekes, M. P., Wills, M. R., Sissons, J. G. P., Carmichael, A. J. (2004). Long-Term Stable Expanded Human CD4+ T Cell Clones Specific for Human Cytomegalovirus Are Distributed in Both CD45RAhigh and CD45ROhigh Populations. J. Immunol. 173: 5843-5851 [Abstract] [Full Text]
Kubota, R., Furukawa, Y., Izumo, S., Usuku, K., Osame, M. (2003). Degenerate specificity of HTLV-1-specific CD8+ T cells during viral replication in patients with HTLV-1-associated myelopathy (HAM/TSP). Blood 101: 3074-3081 [Abstract] [Full Text]
Plumbley, J. A., Fan, H., Eagan, P. A., Ehsan, A., Schnitzer, B., Gulley, M. L. (2002). Lymphoid Tissues from Patients with Infectious Mononucleosis Lack Monoclonal B and T Cells. J. Mol. Diagn. 4: 37-43 [Abstract] [Full Text]
Boon, A. C. M., de Mutsert, G., Graus, Y. M. F., Fouchier, R. A. M., Sintnicolaas, K., Osterhaus, A. D. M. E., Rimmelzwaan, G. F. (2002). The Magnitude and Specificity of Influenza A Virus-Specific Cytotoxic T-Lymphocyte Responses in Humans Is Related to HLA-A and -B Phenotype. J. Virol. 76: 582-590 [Abstract] [Full Text]
Silins, S. L., Sherritt, M. A., Silleri, J. M., Cross, S. M., Elliott, S. L., Bharadwaj, M., Le, T. T. T., Morrison, L. E., Khanna, R., Moss, D. J., Suhrbier, A., Misko, I. S. (2001). Asymptomatic primary Epstein-Barr virus infection occurs in the absence of blood T-cell repertoire perturbations despite high levels of systemic viral load. Blood 98: 3739-3744 [Abstract] [Full Text]
Hislop, A. D., Gudgeon, N. H., Callan, M. F. C., Fazou, C., Hasegawa, H., Salmon, M., Rickinson, A. B. (2001). EBV-Specific CD8+ T Cell Memory: Relationships Between Epitope Specificity, Cell Phenotype, and Immediate Effector Function. J. Immunol. 167: 2019-2029 [Abstract] [Full Text]
Miura, Y., Thoburn, C. J., Bright, E. C., Sommer, M., Lefell, S., Ueda, M., Nakao, S., Hess, A. D. (2001). Characterization of the T-cell repertoire in autologous graft-versus-host disease (GVHD): evidence for the involvement of antigen-driven T-cell response in the development of autologous GVHD. Blood 98: 868-876 [Abstract] [Full Text]
Godthelp, B. C., van Tol, M. J. D., Vossen, J. M., van den Elsen, P. J. (2001). Longitudinal analysis of T cells responding to tetanus toxoid in healthy subjects as well as in pediatric patients after bone marrow transplantation: the identification of identical TCR-CDR3 regions in time suggests long-term stability of at least part of the antigen-specific TCR repertoire. Int Immunol 13: 507-518 [Abstract] [Full Text]
Plunkett, F. J., Soares, M. V. D., Annels, N., Hislop, A., Ivory, K., Lowdell, M., Salmon, M., Rickinson, A., Akbar, A. N. (2001). The flow cytometric analysis of telomere length in antigen-specific CD8+ T cells during acute Epstein-Barr virus infection. Blood 97: 700-707 [Abstract] [Full Text]
Maini, M. K., Gudgeon, N., Wedderburn, L. R., Rickinson, A. B., Beverley, P. C. L. (2000). Clonal Expansions in Acute EBV Infection Are Detectable in the CD8 and not the CD4 Subset and Persist with a Variable CD45 Phenotype. J. Immunol. 165: 5729-5737 [Abstract] [Full Text]
Annels, N. E., Callan, M. F. C., Tan, L., Rickinson, A. B. (2000). Changing Patterns of Dominant TCR Usage with Maturation of an EBV-Specific Cytotoxic T Cell Response. J. Immunol. 165: 4831-4841 [Abstract] [Full Text]
Godthelp, B. C., van Tol, M. J.D., Vossen, J. M., van den Elsen, P. J. (1999). T-Cell Immune Reconstitution in Pediatric Leukemia Patients After Allogeneic Bone Marrow Transplantation With T-Cell-Depleted or Unmanipulated Grafts: Evaluation of Overall and Antigen-Specific T-Cell Repertoires. Blood 94: 4358-4369 [Abstract] [Full Text]
Tanner, J. E., Alfieri, C. (1999). Epstein-Barr Virus Induces Fas (CD95) in T Cells and Fas Ligand in B Cells Leading to T-Cell Apoptosis. Blood 94: 3439-3447 [Abstract] [Full Text]
Kolowos, W., Schmitt, M., Herrman, M., Harrer, E., Low, P., Kalden, J. R., Harrer, T. (1999). Biased TCR Repertoire in HIV-1-Infected Patients Due to Clonal Expansion of HIV-1-Reverse Transcriptase-Specific CTL Clones. J. Immunol. 162: 7525-7533 [Abstract] [Full Text]
Weekes, M. P., Carmichael, A. J., Wills, M. R., Mynard, K., Sissons, J. G. P. (1999). Human CD28-CD8+ T Cells Contain Greatly Expanded Functional Virus-Specific Memory CTL Clones. J. Immunol. 162: 7569-7577 [Abstract] [Full Text]
Zeng, W., Nakao, S., Takamatsu, H., Yachie, A., Takami, A., Kondo, Y., Sugimori, N., Yamazaki, H., Miura, Y., Shiobara, S., Matsuda, T. (1999). Characterization of T-Cell Repertoire of the Bone Marrow in Immune-Mediated Aplastic Anemia: Evidence for the Involvement of Antigen-Driven T-Cell Response in Cyclosporine-Dependent Aplastic Anemia. Blood 93: 3008-3016 [Abstract] [Full Text]
Maini, M. K., Soares, M. V. D., Zilch, C. F., Akbar, A. N., Beverley, P. C. L. (1999). Virus-Induced CD8+ T Cell Clonal Expansion Is Associated with Telomerase Up-Regulation and Telomere Length Preservation: A Mechanism for Rescue from Replicative Senescence. J. Immunol. 162: 4521-4526 [Abstract] [Full Text]
Marten, N. W., Stohlman, S. A., Smith-Begolka, W., Miller, S. D., Dimacali, E., Yao, Q., Stohl, S., Goverman, J., Bergmann, C. C. (1999). Selection of CD8+ T Cells with Highly Focused Specificity During Viral Persistence in the Central Nervous System. J. Immunol. 162: 3905-3914 [Abstract] [Full Text]
Misko, I. S., Cross, S. M., Khanna, R., Elliott, S. L., Schmidt, C., Pye, S. J., Silins, S. L. (1999). Crossreactive recognition of viral, self, and bacterial peptide ligands by human class I-restricted cytotoxic T lymphocyte clonotypes: Implications for molecular mimicry in autoimmune disease. Proc. Natl. Acad. Sci. USA 96: 2279-2284 [Abstract] [Full Text]
Weekes, M. P., Wills, M. R., Mynard, K., Carmichael, A. J., Sissons, J. G.�P. (1999). The Memory Cytotoxic T-Lymphocyte (CTL) Response to Human Cytomegalovirus Infection Contains Individual Peptide-Specific CTL Clones That Have Undergone Extensive Expansion In Vivo. J. Virol. 73: 2099-2108 [Abstract] [Full Text]
Pion, S., Christianson, G. J., Fontaine, P., Roopenian, D. C., Perreault, C. (1999). Shaping the Repertoire of Cytotoxic T-Lymphocyte Responses: Explanation for the Immunodominance Effect Whereby Cytotoxic T Lymphocytes Specific for Immunodominant Antigens Prevent Recognition of Nondominant Antigens. Blood 93: 952-962 [Abstract] [Full Text]
Ishikawa, T., Kono, D., Chung, J., Fowler, P., Theofilopoulos, A., Kakumu, S., Chisari, F. V. (1998). Polyclonality and Multispecificity of the CTL Response to a Single Viral Epitope. J. Immunol. 161: 5842-5850 [Abstract] [Full Text]
Levitsky, V., de Campos-Lima, P.-O., Frisan, T., Masucci, M. G. (1998). The Clonal Composition of a Peptide-Specific Oligoclonal CTL Repertoire Selected in Response to Persistent EBV Infection Is Stable Over Time. J. Immunol. 161: 594-601 [Abstract] [Full Text]
Sourdive, D. J.D., Murali-Krishna, K., Altman, J. D., Zajac, A. J., Whitmire, J. K., Pannetier, C., Kourilsky, P., Evavold, B., Sette, A., Ahmed, R. (1998). Conserved T Cell Receptor Repertoire in Primary and Memory CD8 T Cell Responses to an Acute Viral Infection. J. Exp. Med. 188: 71-82 [Abstract] [Full Text]
McMichael, A. J., O'Callaghan, C. A. (1998). A New Look at T Cells. J. Exp. Med. 187: 1367-1371 [Full Text]
Campos-Lima, P.-O. d., Levitsky, V., Imreh, M. P., Gavioli, R., Masucci, M. G. (1997). Epitope-dependent Selection of Highly Restricted or Diverse T Cell Receptor Repertoires in Response to Persistent Infection by Epstein-Barr Virus. J. Exp. Med. 186: 83-89 [Abstract] [Full Text]