Longitudinal analysis of T cell receptor (TCR) gene usage by human immunodeficiency virus 1 envelope-specific cytotoxic T lymphocyte clones reveals a limited TCR repertoire

doi:10.1084/jem.179.4.1261

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 Kalams, S. A.
	Articles by Walker, B. D.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Kalams, S. A.
	Articles by Walker, B. D.


Social Bookmarking

	What's this?

ARTICLES

Longitudinal analysis of T cell receptor (TCR) gene usage by human immunodeficiency virus 1 envelope-specific cytotoxic T lymphocyte clones reveals a limited TCR repertoire

SA Kalams, RP Johnson, AK Trocha, MJ Dynan, HS Ngo, RT D'Aquila, JT Kurnick and BD Walker
Infectious Disease Unit, Massachusetts General Hospital, Boston.

Human immunodeficiency virus 1 (HIV-1) infection is associated with a vigorous cellular immune response that allows detection of cytotoxic T lymphocyte (CTL) activity using freshly isolated peripheral blood mononuclear cells (PBMC). Although restricting class I antigens and epitopes recognized by HIV-1-specific CTL have been defined, the effector cells mediating this vigorous response have been characterized less well. Specifically, no studies have addressed the breadth and duration of response to a defined epitope. In the present study, a longitudinal analysis of T cell receptor (TCR) gene usage by CTL clones was performed in a seropositive person using TCR gene sequences as a means of tracking responses to a well-defined epitope in the glycoprotein 41 transmembrane protein. 10 CTL clones specific for this human histocompatibility leukocyte antigen-B14-restricted epitope were isolated at multiple time points over a 31-mo period. All clones were derived from a single asymptomatic HIV-1-infected individual with a vigorous response to this epitope that was detectable using unstimulated PBMC. Polymerase chain reaction amplification using V alpha and V beta family-specific primers was performed on each clone, followed by DNA sequencing of the V-D-J regions. All 10 clones utilized V alpha 14 and V beta 4 genes. Sequence analysis of the TCR revealed the first nine clones isolated to also be identical at the nucleotide level. The TCR-alpha junctional region sequence of the tenth clone was identical to the junctional region sequences of the other nine, but this clone utilized distinct D beta and J beta gene segments. This study provides evidence that the observed high degree of HIV-1-specific CTL activity may be due to monoclonal or oligoclonal expansion of specific effector cells, and that progeny of a particular CTL clone may persist for prolonged periods in vivo in the presence of a chronic productive viral infection. The observed limited TCR diversity against an immunodominant epitope may limit recognition of virus variants with mutations in regions interacting with the TCR, thereby facilitating immune escape.
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:

Ramalingam, R. K., Meyer-Olson, D., Shoukry, N. H., Bowen, D. G., Walker, C. M., Kalams, S. A. (2008). Kinetic Analysis by Real-Time PCR of Hepatitis C Virus (HCV)-Specific T Cells in Peripheral Blood and Liver after Challenge with HCV. J. Virol. 82: 10487-10492 [Abstract] [Full Text]
Grotenbreg, G. M., Roan, N. R., Guillen, E., Meijers, R., Wang, J.-h., Bell, G. W., Starnbach, M. N., Ploegh, H. L. (2008). Discovery of CD8+ T cell epitopes in Chlamydia trachomatis infection through use of caged class I MHC tetramers. Proc. Natl. Acad. Sci. USA 105: 3831-3836 [Abstract] [Full Text]
Sen, P., Charini, W. A., Subbramanian, R. A., Manuel, E. R., Kuroda, M. J., Autissier, P. A., Letvin, N. L. (2008). Clonal Focusing of Epitope-Specific CD8+ T Lymphocytes in Rhesus Monkeys following Vaccination and Simian-Human Immunodeficiency Virus Challenge. J. Virol. 82: 805-816 [Abstract] [Full Text]
Day, E. K., Carmichael, A. J., ten Berge, I. J. M., Waller, E. C. P., Sissons, J. G. P., Wills, M. R. (2007). Rapid CD8+ T Cell Repertoire Focusing and Selection of High-Affinity Clones into Memory Following Primary Infection with a Persistent Human Virus: Human Cytomegalovirus. J. Immunol. 179: 3203-3213 [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]
Appanna, R., Huat, T. L., See, L. L. C., Tan, P. L., Vadivelu, J., Devi, S. (2007). Cross-Reactive T-Cell Responses to the Nonstructural Regions of Dengue Viruses among Dengue Fever and Dengue Hemorrhagic Fever Patients in Malaysia. CVI 14: 969-977 [Abstract] [Full Text]
Yang, H., Dong, T., Turnbull, E., Ranasinghe, S., Ondondo, B., Goonetilleke, N., Winstone, N., di Gleria, K., Bowness, P., Conlon, C., Borrow, P., Hanke, T., McMichael, A., Dorrell, L. (2007). Broad TCR Usage in Functional HIV-1-Specific CD8+ T Cell Expansions Driven by Vaccination during Highly Active Antiretroviral Therapy. J. Immunol. 179: 597-606 [Abstract] [Full Text]
Miles, J. J., Borg, N. A., Brennan, R. M., Tynan, F. E., Kjer-Nielsen, L., Silins, S. L., Bell, M. J., Burrows, J. M., McCluskey, J., Rossjohn, J., Burrows, S. R. (2006). TCR{alpha} Genes Direct MHC Restriction in the Potent Human T Cell Response to a Class I-Bound Viral Epitope. J. Immunol. 177: 6804-6814 [Abstract] [Full Text]
Speiser, D. E., Baumgaertner, P., Barbey, C., Rubio-Godoy, V., Moulin, A., Corthesy, P., Devevre, E., Dietrich, P.-Y., Rimoldi, D., Lienard, D., Cerottini, J.-C., Romero, P., Rufer, N. (2006). A Novel Approach to Characterize Clonality and Differentiation of Human Melanoma-Specific T Cell Responses: Spontaneous Priming and Efficient Boosting by Vaccination. J. Immunol. 177: 1338-1348 [Abstract] [Full Text]
Turnbull, E. L., Lopes, A. R., Jones, N. A., Cornforth, D., Newton, P., Aldam, D., Pellegrino, P., Turner, J., Williams, I., Wilson, C. M., Goepfert, P. A., Maini, M. K., Borrow, P. (2006). HIV-1 Epitope-Specific CD8+ T Cell Responses Strongly Associated with Delayed Disease Progression Cross-Recognize Epitope Variants Efficiently. J. Immunol. 176: 6130-6146 [Abstract] [Full Text]
Meyer-Olson, D., Brady, K. W., Bartman, M. T., O'Sullivan, K. M., Simons, B. C., Conrad, J. A., Duncan, C. B., Lorey, S., Siddique, A., Draenert, R., Addo, M., Altfeld, M., Rosenberg, E., Allen, T. M., Walker, B. D., Kalams, S. A. (2006). Fluctuations of functionally distinct CD8+ T-cell clonotypes demonstrate flexibility of the HIV-specific TCR repertoire. Blood 107: 2373-2383 [Abstract] [Full Text]
Ruckert, C., Fiorillo, M. T., Loll, B., Moretti, R., Biesiadka, J., Saenger, W., Ziegler, A., Sorrentino, R., Uchanska-Ziegler, B. (2006). Conformational Dimorphism of Self-peptides and Molecular Mimicry in a Disease-associated HLA-B27 Subtype. J. Biol. Chem. 281: 2306-2316 [Abstract] [Full Text]
Miles, J. J., Elhassen, D., Borg, N. A., Silins, S. L., Tynan, F. E., Burrows, J. M., Purcell, A. W., Kjer-Nielsen, L., Rossjohn, J., Burrows, S. R., McCluskey, J. (2005). CTL Recognition of a Bulged Viral Peptide Involves Biased TCR Selection. J. Immunol. 175: 3826-3834 [Abstract] [Full Text]
Fiorillo, M. T., Ruckert, C., Hulsmeyer, M., Sorrentino, R., Saenger, W., Ziegler, A., Uchanska-Ziegler, B. (2005). Allele-dependent Similarity between Viral and Self-peptide Presentation by HLA-B27 Subtypes. J. Biol. Chem. 280: 2962-2971 [Abstract] [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]
Leggatt, G. R., Narayan, S., Fernando, G. J. P., Frazer, I. H. (2004). Changes to peptide structure, not concentration, contribute to expansion of the lowest avidity cytotoxic T lymphocytes. J. Leukoc. Biol. 76: 787-795 [Abstract] [Full Text]
Lopes, A. R., Jaye, A., Dorrell, L., Sabally, S., Alabi, A., Jones, N. A., Flower, D. R., De Groot, A., Newton, P., Lascar, R. M., Williams, I., Whittle, H., Bertoletti, A., Borrow, P., Maini, M. K. (2003). Greater CD8+ TCR Heterogeneity and Functional Flexibility in HIV-2 Compared to HIV-1 Infection. J. Immunol. 171: 307-316 [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]
Valmori, D., Dutoit, V., Schnuriger, V., Quiquerez, A.-L., Pittet, M. J., Guillaume, P., Rubio-Godoy, V., Walker, P. R., Rimoldi, D., Lienard, D., Cerottini, J.-C., Romero, P., Dietrich, P.-Y. (2002). Vaccination with a Melan-A Peptide Selects an Oligoclonal T Cell Population with Increased Functional Avidity and Tumor Reactivity. J. Immunol. 168: 4231-4240 [Abstract] [Full Text]
Douek, D. C., Betts, M. R., Brenchley, J. M., Hill, B. J., Ambrozak, D. R., Ngai, K.-L., Karandikar, N. J., Casazza, J. P., Koup, R. A. (2002). A Novel Approach to the Analysis of Specificity, Clonality, and Frequency of HIV-Specific T Cell Responses Reveals a Potential Mechanism for Control of Viral Escape. J. Immunol. 168: 3099-3104 [Abstract] [Full Text]
Lawson, T. M., Man, S., Williams, S., Boon, A. C. M., Zambon, M., Borysiewicz, L. K. (2001). Influenza A antigen exposure selects dominant V{beta}17+ TCR in human CD8+ cytotoxic T cell responses. Int Immunol 13: 1373-1381 [Abstract] [Full Text]
Dutoit, V., Rubio-Godoy, V., Dietrich, P.-Y., Quiqueres, A.-L., Schnuriger, V., Rimoldi, D., Lienard, D., Speiser, D., Guillaume, P., Batard, P., Cerottini, J.-C., Romero, P., Valmori, D. (2001). Heterogeneous T-Cell Response to MAGE-A10254-262: High Avidity-specific Cytolytic T Lymphocytes Show Superior Antitumor Activity. Cancer Res. 61: 5850-5856 [Abstract] [Full Text]
Bitmansour, A. D., Waldrop, S. L., Pitcher, C. J., Khatamzas, E., Kern, F., Maino, V. C., Picker, L. J. (2001). Clonotypic Structure of the Human CD4+ Memory T Cell Response to Cytomegalovirus. J. Immunol. 167: 1151-1163 [Abstract] [Full Text]
Islam, S. A., Hay, C. M., Hartman, K. E., He, S., Shea, A. K., Trocha, A. K., Dynan, M. J., Reshamwala, N., Buchbinder, S. P., Basgoz, N. O., Kalams, S. A. (2001). Persistence of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T-Lymphocyte Clones in a Subject with Rapid Disease Progression. J. Virol. 75: 4907-4911 [Abstract] [Full Text]
Clay, T. M., Hobeika, A. C., Mosca, P. J., Lyerly, H. K., Morse, M. A. (2001). Assays for Monitoring Cellular Immune Responses to Active Immunotherapy of Cancer. Clin. Cancer Res. 7: 1127-1135 [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]
Chen, Z. W., Li, Y., Zeng, X., Kuroda, M. J., Schmitz, J. E., Shen, Y., Lai, X., Shen, L., Letvin, N. L. (2001). The TCR Repertoire of an Immunodominant CD8+ T Lymphocyte Population. J. Immunol. 166: 4525-4533 [Abstract] [Full Text]
Schito, A. M., Vittinghoff, E., Hecht, F. M., Elkins, M. K., Kahn, J. O., Levy, J. A., Oksenberg, J. R. (2001). Longitudinal analysis of T-cell receptor gene use by CD8+ T cells in early human immunodeficiency virus infection in patients receiving highly active antiretroviral therapy. Blood 97: 214-220 [Abstract] [Full Text]
Posavad, C. M., Huang, M. L., Barcy, S., Koelle, D. M., Corey, L. (2000). Long Term Persistence of Herpes Simplex Virus-Specific CD8+ CTL in Persons with Frequently Recurring Genital Herpes. J. Immunol. 165: 1146-1152 [Abstract] [Full Text]
Appay, V., Nixon, D. F., Donahoe, S. M., Gillespie, G. M.A., Dong, T., King, A., Ogg, G. S., Spiegel, H. M.L., Conlon, C., Spina, C. A., Havlir, D. V., Richman, D. D., Waters, A., Easterbrook, P., McMichael, A. J., Rowland-Jones, S. L. (2000). HIV-specific CD8+ T Cells Produce Antiviral Cytokines but Are Impaired in Cytolytic Function. JEM 192: 63-76 [Abstract] [Full Text]
Valmori, D., Dutoit, V., Lienard, D., Lejeune, F., Speiser, D., Rimoldi, D., Cerundolo, V., Dietrich, P.-Y., Cerottini, J.-C., Romero, P. (2000). Tetramer-Guided Analysis of TCR {beta}-Chain Usage Reveals a Large Repertoire of Melan-A-Specific CD8+ T Cells in Melanoma Patients. J. Immunol. 165: 533-538 [Abstract] [Full Text]
Whiteside, T. L. (2000). Monitoring of Antigen-Specific Cytolytic T Lymphocytes in Cancer Patients Receiving Immunotherapy. CVI 7: 327-332 [Full Text]
Chisari, F. V. (2000). Viruses, Immunity, and Cancer: Lessons from Hepatitis B. Am. J. Pathol. 156: 1117-1132 [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]
Ogg, G. S., Kostense, S., Klein, M. R., Jurriaans, S., Hamann, D., McMichael, A. J., Miedema, F. (1999). Longitudinal Phenotypic Analysis of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes: Correlation with Disease Progression. J. Virol. 73: 9153-9160 [Abstract] [Full Text]
Dalod, M., Dupuis, M., Deschemin, J.-C., Sicard, D., Salmon, D., Delfraissy, J.-F., Venet, A., Sinet, M., Guillet, J.-G. (1999). Broad, Intense Anti-Human Immunodeficiency Virus (HIV) Ex Vivo CD8+ Responses in HIV Type 1-Infected Patients: Comparison with Anti-Epstein-Barr Virus Responses and Changes during Antiretroviral Therapy. J. Virol. 73: 7108-7116 [Abstract] [Full Text]
Kalams, S. A., Buchbinder, S. P., Rosenberg, E. S., Billingsley, J. M., Colbert, D. S., Jones, N. G., Shea, A. K., Trocha, A. K., Walker, B. D. (1999). Association between Virus-Specific Cytotoxic T-Lymphocyte and Helper Responses in Human Immunodeficiency Virus Type 1 Infection. J. Virol. 73: 6715-6720 [Abstract] [Full Text]
Kalams, S. A., Goulder, P. J., Shea, A. K., Jones, N. G., Trocha, A. K., Ogg, G. S., Walker, B. D. (1999). Levels of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T-Lymphocyte Effector and Memory Responses Decline after Suppression of Viremia with Highly Active Antiretroviral Therapy. J. Virol. 73: 6721-6728 [Abstract] [Full Text]
Hay, C. M., Ruhl, D. J., Basgoz, N. O., Wilson, C. C., Billingsley, J. M., DePasquale, M. P., D'Aquila, R. T., Wolinsky, S. M., Crawford, J. M., Montefiori, D. C., Walker, B. D. (1999). Lack of Viral Escape and Defective In Vivo Activation of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes in Rapidly Progressive Infection. J. Virol. 73: 5509-5519 [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]
Brander, C., Goulder, P. J. R., Luzuriaga, K., Yang, O. O., Hartman, K. E., Jones, N. G., Walker, B. D., Kalams, S. A. (1999). Persistent HIV-1-Specific CTL Clonal Expansion Despite High Viral Burden Post In Utero HIV-1 Infection. J. Immunol. 162: 4796-4800 [Abstract] [Full Text]
Nikolic, B., Gardner, J. P., Scadden, D. T., Arn, J. S., Sachs, D. H., Sykes, M. (1999). Normal Development in Porcine Thymus Grafts and Specific Tolerance of Human T Cells to Porcine Donor MHC. J. Immunol. 162: 3402-3407 [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]
Gray, C. M., Lawrence, J., Schapiro, J. M., Altman, J. D., Winters, M. A., Crompton, M., Loi, M., Kundu, S. K., Davis, M. M., Merigan, T. C. (1999). Frequency of Class I HLA-Restricted Anti-HIV CD8+ T Cells in Individuals Receiving Highly Active Antiretroviral Therapy (HAART). J. Immunol. 162: 1780-1788 [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]
Steele, J. C., Young, S. P., Goodall, J. C., Gallimore, P. H. (1998). Structural Aspects of the Interaction Between Heterogeneic Human Papillomavirus Type 1 E4-Specific T Cell Receptors and the Same Peptide/HLA-DQ8 Complex. J. Immunol. 161: 4745-4752 [Abstract] [Full Text]
Quayle, A. J., Coston, W. M. P., K. Trocha, A., Kalams, S. A., Mayer, K. H., Anderson, D. J. (1998). Detection of HIV-1-Specific CTLs in the Semen of HIV-Infected Individuals. J. Immunol. 161: 4406-4410 [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]
McMichael, A. J., O'Callaghan, C. A. (1998). A New Look at T Cells. JEM 187: 1367-1371 [Full Text]
Bertoletti, A., Cham, F., McAdam, S., Rostron, T., Rowland-Jones, S., Sabally, S., Corrah, T., Ariyoshi, K., Whittle, H. (1998). Cytotoxic T Cells from Human Immunodeficiency Virus Type 2-Infected Patients Frequently Cross-React with Different Human Immunodeficiency Virus Type 1�Clades. J. Virol. 72: 2439-2448 [Abstract] [Full Text]
Hanke, T, Blanchard, T., Schneider, J, Ogg, G., Tan, R, Becker, M, Gilbert, S., Hill, A., Smith, G., McMichael, A (1998). Immunogenicities of intravenous and intramuscular administrations of modified vaccinia virus Ankara-based multi-CTL epitope vaccine for human immunodeficiency virus type 1 in mice. J. Gen. Virol. 79: 83-90 [Abstract]
Nelson, G. W., Kaslow, R., Mann, D. L. (1997). Frequency of HLA allele-specific peptide motifs in HIV-1 proteins correlates with the allele's association with relative rates of disease progression after HIV-1�infection. Proc. Natl. Acad. Sci. USA 94: 9802-9807 [Abstract] [Full Text]