| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
*
AIDS Research Center and Infectious Disease Unit, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129; and
Department of Pediatrics, University of Massachusetts Medical School, Worcester, MA 01605
To address the issue of clonal exhaustion in humans, we monitored HLA class I-restricted, epitope-specific CTL responses in an in utero HIV-1-infected infant from 3 mo through 5 years of age. Serial functional CTL precursor assays demonstrated persistent, vigorous, and broadly directed HIV-1 specific CTL activity with a dominant response against an epitope in HIV-1 Gag-p17 (SLYNTVATL, aa 77–85). A clonal CTL response directed against the immunodominant, HLA-A*0201-restricted epitope was found to persist over the entire observation period, as shown by TCR analysis of cDNA libraries generated from PBMC. The analysis of autologous viral sequences did not reveal any escape mutations within the targeted epitope, and viral load measurement indicated ongoing viral replication. Furthermore, inhibition of viral replication assays indicated that the epitope was properly processed from autologous viral protein. These data demonstrate that persistent exposure to high levels of viral Ag does not necessarily lead to clonal exhaustion and that epitope-specific clonal CTL responses induced within the first weeks of life can persist for years without inducing detectable viral escape variants.
This article has been cited by other articles:
|
|
 |
|
  P. Sen, W. A. Charini, R. A. Subbramanian, E. R. Manuel, M. J. Kuroda, P. A. Autissier, and N. L. Letvin Clonal Focusing of Epitope-Specific CD8+ T Lymphocytes in Rhesus Monkeys following Vaccination and Simian-Human Immunodeficiency Virus Challenge J. Virol., January 15, 2008; 82(2): 805 - 816. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Pillay, H.-T. Zhang, J. W. Drijfhout, N. Robinson, H. Brown, M. Khan, J. Moodley, M. Adhikari, K. Pfafferott, M. E. Feeney, et al. Unique Acquisition of Cytotoxic T-Lymphocyte Escape Mutants in Infant Human Immunodeficiency Virus Type 1 Infection J. Virol., September 15, 2005; 79(18): 12100 - 12105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Meyer-Olson, N. H. Shoukry, K. W. Brady, H. Kim, D. P. Olson, K. Hartman, A. K. Shintani, C. M. Walker, and S. A. Kalams Limited T Cell Receptor Diversity of HCV-specific T Cell Responses Is Associated with CTL Escape J. Exp. Med., August 2, 2004; 200(3): 307 - 319. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. SenGupta, P. J. Norris, T. J. Suscovich, M. Hassan-Zahraee, H. F. Moffett, A. Trocha, R. Draenert, P. J. R. Goulder, R. J. Binder, D. L. Levey, et al. Heat Shock Protein-Mediated Cross-Presentation of Exogenous HIV Antigen on HLA Class I and Class II J. Immunol., August 1, 2004; 173(3): 1987 - 1993. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Daftarian, S. Ali, R. Sharan, S. F. Lacey, C. La Rosa, J. Longmate, C. Buck, R. F. Siliciano, and D. J. Diamond Immunization with Th-CTL Fusion Peptide and Cytosine-Phosphate-Guanine DNA in Transgenic HLA-A2 Mice Induces Recognition of HIV-Infected T Cells and Clears Vaccinia Virus Challenge J. Immunol., October 15, 2003; 171(8): 4028 - 4039. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Alter, G. Hatzakis, C. M. Tsoukas, K. Pelley, D. Rouleau, R. LeBlanc, J.-G. Baril, H. Dion, E. Lefebvre, R. Thomas, et al. Longitudinal Assessment of Changes in HIV-Specific Effector Activity in HIV-Infected Patients Starting Highly Active Antiretroviral Therapy in Primary Infection J. Immunol., July 1, 2003; 171(1): 477 - 488. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Brenchley, N. J. Karandikar, M. R. Betts, D. R. Ambrozak, B. J. Hill, L. E. Crotty, J. P. Casazza, J. Kuruppu, S. A. Migueles, M. Connors, et al. Expression of CD57 defines replicative senescence and antigen-induced apoptotic death of CD8+ T cells Blood, April 1, 2003; 101(7): 2711 - 2720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Allen, P. Jing, B. Calore, H. Horton, D. H. O'Connor, T. Hanke, M. Piekarczyk, R. Ruddersdorf, B. R. Mothe, C. Emerson, et al. Effects of Cytotoxic T Lymphocytes (CTL) Directed against a Single Simian Immunodeficiency Virus (SIV) Gag CTL Epitope on the Course of SIVmac239 Infection J. Virol., September 11, 2002; 76(20): 10507 - 10511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Islam, C. M. Hay, K. E. Hartman, S. He, A. K. Shea, A. K. Trocha, M. J. Dynan, N. Reshamwala, S. P. Buchbinder, N. O. Basgoz, et al. Persistence of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T-Lymphocyte Clones in a Subject with Rapid Disease Progression J. Virol., May 15, 2001; 75(10): 4907 - 4911. [Abstract] [Full Text]
|
|
|
|
|
|
K. Luzuriaga, M. McManus, M. Catalina, S. Mayack, M. Sharkey, and M. Stevenson Early Therapy of Vertical Human Immunodeficiency Virus Type 1 (HIV-1) Infection: Control of Viral Replication and Absence of Persistent HIV-1-Specific Immune Responses J. Virol., August 1, 2000; 74(15): 6984 - 6991. [Abstract] [Full Text]
|
|
|
|
|
|
M. Dalod, M. Dupuis, J.-C. Deschemin, D. Sicard, D. Salmon, J.-F. Delfraissy, A. Venet, M. Sinet, and J.-G. Guillet 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., September 1, 1999; 73(9): 7108 - 7116. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
