Tracking T cells with tetramers: New tales from new tools

Nature Reviews Immunology

Volumn 2, Issue 4, 2002, Pages 263-272

  Klenerman, Paul ^a   Cerundolo, Vincenzo ^b   Dunbar, P Rod ^b  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b JOHN RADCLIFFE HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

MAJOR HISTOCOMPATIBILITY ANTIGEN; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; PEPTIDE; TETRAMER; BETA 2 MICROGLOBULIN; DYES, REAGENTS, INDICATORS, MARKERS AND BUFFERS; HLA ANTIGEN CLASS 1; LYMPHOCYTE ANTIGEN RECEPTOR; STREPTAVIDIN;

ANIMAL CELL; ANTIGEN SPECIFICITY; BYSTANDER ACTIVATION; BYSTANDER EFFECT; CANCER; CELLULAR IMMUNITY; CROSS PRESENTATION; ENZYME LINKED IMMUNOSPOT ASSAY; HUMAN; HUMAN CELL; IMMUNE RESPONSE; IMMUNOASSAY; IMMUNOLOGICAL IGNORANCE; IMMUNOLOGICAL TOLERANCE; INFECTION; INTRACELLULAR CYTOKINE STAIN; LYMPHOCYTE ACTIVATION; LYMPHOCYTE COUNT; LYMPHOCYTE FUNCTION; MAJOR HISTOCOMPATIBILITY COMPLEX; MEMORY CELL; NATURAL KILLER CELL; NATURAL KILLER T CELL; NONHUMAN; PHENOTYPIC VARIATION; PRIORITY JOURNAL; REVIEW; STAINING; T LYMPHOCYTE; TUMOR IMMUNOLOGY; ANIMAL; DISEASE MODEL; IMMUNOLOGY; MACROMOLECULE; NEOPLASM; VIRUS INFECTION;

ANIMALS; BETA 2-MICROGLOBULIN; DISEASE MODELS, ANIMAL; HISTOCOMPATIBILITY ANTIGENS CLASS I; HUMANS; IMMUNITY, CELLULAR; INDICATORS AND REAGENTS; LYMPHOCYTE COUNT; MACROMOLECULAR SUBSTANCES; NEOPLASMS; PEPTIDES; RECEPTORS, ANTIGEN, T-CELL; STREPTAVIDIN; T-LYMPHOCYTES; VIRUS DISEASES;

EID: 0036549509     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri777     Document Type: Review

References (109)

1. Ogg, G. S. & McMichael, A. J. HLA-peptide tetrameric complexes. Curr. Opin. Immunol. 10, 393-396 (1998).
2. McMichael, A. J. & O'Callaghan, C. A. A new look at T cells. J. Exp. Med. 187, 1367-1371 (1998).
3. + lymphocytes using class I peptide tetramers. Rev. Med. Virol. 11, 11-22 (2001).
4. Doherty, P. C., Christensen, J. P., Belz, G. T., Stevenson, P. G. & Sangster, M. Y. Dissecting the host response to a γ-herpesvirus. Phil. Trans. R. Soc. Lond. B Biol. Sci. 356, 581-593 (2001). Describes the fundamental differences between a persistent and non-persistent mouse pathogen.
5. Altman, J. et al. Direct visualization and phenotypic analysis of virus-specific T lymphocytes in HIV-infected individuals. Science 274, 94-96 (1996). Now a classic paper, this was the first to describe the use of tetramers for ex vivo phenotyping.
6. Murali-Krishna, K. et al. Counting antigen-specific CD8 T cells: a reevaluation of bystander activation during viral infection. Immunity 8, 177-187 (1998).
7. Gallimore, A. et al. Induction and exhaustion of lymphocytic-choriomeningitis-virus-specific cytotoxic T lymphocytes visualized using soluble tetrameric major histocompatibility complex class-I-peptide complexes. J. Exp. Med. 187, 1383-1393 (1998).
8. Masopust, D., Vezys, V., Marzo, A. & Lefrancois, L. Preferential localisation of effector memory cells in nonlymphoid tissue. Science 291, 2413-2417 (2001). Reveals the unexpected finding that T-cell memory, even after very brief infections, can maintain readily activated T cells in non-lymphoid organs, such as lung and liver.
9. + T cells in primary and secondary influenza pneumonia. Immunity 8, 683-691 (1998).
10. + T cells over time.
11. + T-cell selection, function and death in the primary immune response in vivo. J. Clin. Invest. 106, 1251-1261 (2000).
12. + T cells during the primary immune response to Epstein-Barr virus in vivo. J. Exp. Med. 187, 1395-1402 (1998).
13. Wilson, J. D. et al. Direct visualization of HIV-1-specific cytotoxic T lymphocytes during primary infection. AIDS 14, 225-233 (2000).
14. Lechner, F. et al. Analysis of successful immune responses in persons infected with hepatitis C virus. J. Exp. Med. 191, 1499-1512 (2000).
15. Lechner, F. et al. CTL responses are induced during acute HCV infection but are not sustained. Eur. J. Immunol. 30, 2479-2487 (2000).
16. + T cells associated with the control of infection. Gastroenterology 117, 1386-1396 (1999).
17. + lymphocytes from simian-immunodeficiency-virus-infected rhesus macaques recognize 14 different epitopes bound by the major histocompatibility complex class I molecule mamu-A*01: implications for vaccine design and testing. J. Virol. 75, 738-749 (2001).
18. Kuroda, M. J. et al. Emergence of CTL coincides with clearance of virus during primary simian immunodeficiency virus infection in rhesus monkeys. J. Immunol. 162, 5127-5133 (1999).
19. Crispe, I., Dao, T., Klugewitz, K., Mehal, W. & Metz, D. The liver as a site of T-cell apoptosis: graveyard or killing field? Immunol. Rev. 174, 47-62 (2000).
20. Schmitz, J. E. et al. Simian immunodeficiency virus (SIV)-specific CTL are present in large numbers in livers of SIV-infected Rhesus monkeys. J. Immunol. 164, 6015-6019 (2000).
21. + T cells in the liver during control and resolution phases of influenza pneumonia. Proc. Natl Acad. Sci. USA 95, 1382-1387 (1998).
22. Zajac, A. et al. Viral immune evasion due to persistence of activated T cells without effector function. J. Exp. Med. 188, 2205-2213 (1998).
23. Ogg, G. S. et al. Decay kinetics of human-immunodeficiency-virus-specific effector cytotoxic T lymphocytes after combination antiretroviral therapy J. Virol. 73, 797-600 (1999).
24. Andre, P. et al. An HIV-1 protease inhibitor modulates proteasome function, antigen presentation and CTL responses in vivo. Proc. Natl Acad. Sci. 95, 13120-13124 (1999).
25. + T lymphocytes in healthy seropositive donors. J. Virol. 74, 8140-8150 (2000).
26. + T cells specific for EBV in healthy virus carriers. J. Immunol. 162, 1827-1835 (1999). Describes the phenotype of virus-specific cells during long-term suppression of virus in a truly persistent infection, Epstein-Barr virus. Also describes the reactivation of EBV-specific populations during viral recrudescence without overt symptoms.
27. + T lymphocytes. J. Virol. 75, 540-543 (2001). Also describes the reactivation of EBV-specific populations during viral recrudescence without overt symptoms.
28. Dunbar, P. R. et al. Direct isolation, phenotyping and cloning of low-frequency antigen-specific cytotoxic T lymphocytes from peripheral blood. Curr. Biol. 8, 413-416 (1998).
29. Goulder, P. J., Lechner, F., Klenerman, P., McIntosh, K. & Walker, B. D. Characterization of a novel respiratory syncytial virus-specific human cytotoxic T-lymphocyte epitope. J. Virol. 74, 7694-7697 (2000).
30. + T lymphocytes. Clin. Exp. Immunol. 125, 432-439 (2001).
31. + T-cell memory: relationships between epitope specificity, cell phenotype and immediate effector function. J. Immunol. 167, 2019-2029 (2001).
32. Champagne, P. et al. Skewed maturation of memory HIV-specific CD8 T lymphocytes. Nature 410, 106-111 (2001).
33. + T cells vary in differentiation phenotype in different persistent virus infections. Nature Med. 8, 379-385.
34. Lauvau, G. et al. Priming of memory but not effector CD8 T cells by a killed bacterial vaccine. Science 294, 1735-1739 (2001). In vivo study linking changes in T-cell phenotype with protective function.
35. + T cells in peripheral blood and liver using peptide-MHC tetramers. Proc. Natl Acad. Sci. USA 96, 5692-5697 (1999).
36. Grabowska, A. M. et al. Direct ex vivo comparison of the breadth and specificity of the T cells in the liver and peripheral blood of patients with chronic HCV infection. Eur. J. Immunol. 31, 2388-2394 (2001).
37. + cells in liver damage and viral control during persistent hepatitis B virus infection. J. Exp. Med. 191, 1269-1280 (2000).
38. Ou, R., Zhou, S., Huang, L. & Moskophidis, D. Critical role for α/β and γ interferons in persistence of LCMV by clonal exhaustion of CTL. J. Virol. 75, 8407-8423 (2001). Highly comprehensive dissection of tetramer staining versus functional assays in the mouse LCMV model. Reveals the time-course of response and resolves discrepancies between assays.
39. Thimme, R. et al. Determinants of acute viral clearance and persistence during acute HCV infection. J. Exp. Med. 194, 1395-1406 (2001).
40. + T lymphocytes and increased EBV load in HIV-1-infected individuals progressing to AIDS-related non-Hodgkin lymphoma. Blood 98, 146-155 (2001).
41. + T-cell expansions: evidence for impaired CTL effector function. Eur. J. Immunol. 31, 677-686 (2001).
42. Boni, C. et al. Lamivudine treatment can overcome cytotoxic T-cell hyporesponsiveness in chronic hepatitis B: new perspectives for immune therapy. Hepatology 33, 963-971 (2001).
43. Boon, T. & Old, L. J. Cancer tumor antigens. Curr. Opin. Immunol. 9, 681-683 (1997).
44. Molldrem, J. J. et al. Evidence that specific T lymphocytes may participate in the elimination of chronic myelogenous leukemia. Nature Med. 6, 1018-1023 (2000). Describes the first use of tetramers in analysis of CML, potentially opening the field in new directions with regards to malignancy.
45. Romero, P. et al. Ex vivo staining of metastatic lymph nodes by class I major histocompatibility complex tetramers reveals high numbers of antigen-experienced tumor-specific cytolytic T lymphocytes. J. Exp. Med. 188, 1641-1650 (1998).
46. Dunbar, P. P. et al. A shift in the phenotype of melan-A-specific CTL identifies melanoma patients with an active tumor-specific immune response. J. Immunol. 165, 6644-6652 (2000).
47. Anichini, A. et al. An expanded peripheral T-cell population to a cytotoxic T lymphocyte (CTL)-defined, melanocyte-specific antigen in metastatic melanoma patients impacts on generation of peptide-specific CTLs but does not overcome tumor escape from immune surveillance in metastatic lesions. J. Med. 190, 651-668 (1999).
48. Lee, P. P. et al. Characterization of circulating T cells specific for tumor-associated antigens in melanoma patients. Nature Med. 5, 677-685 (1999).
49. Palermo, B. et al. Diverse expansion potential and heterogeneous avidity in tumor-associated antigen-specific T lymphocytes from primary melanoma patients. Eur. J. Immunol. 31, 412-420 (2001).
50. Valmori, D. et al. Analysis of the cytolytic T lymphocyte response of melanoma patients to the naturally HLA-A*0201-associated tyrosinase peptide 368-376. Cancer Res. 59, 4050-4055 (1999).
51. Coulie, P. G. et al. A monoclonal cytolytic T-lymphocyte response observed in a melanoma patient vaccinated with a tumor-specific antigenic peptide encoded by gene MAGE-3. Proc. Natl Acad. Sci. USA 98, 10290-10295 (2001).
52. Kawakami, Y. et al. Cloning of the gene coding for a shared human melanoma antigen recognized by autologous T cells infiltrating into tumor. Proc. Natl Acad. Sci. USA 91, 3515-3519 (1994).
53. Jager, E. et al. Monitoring CD8 T-cell responses to NY-ESO-1: correlation of humoral and cellular immune responses. Proc. Natl Acad. Sci. USA 97, 4760-4765 (2000).
54. Dutoit, V. et al. Heterogeneous T-cell response to MAGE-A10(284-262): high-avidity-specific cytolytic T lymphocytes show superior antitumor activity. Cancer Res. 61, 5850-5856 (2001).
55. Speiser, D. E. et al. Self antigens expressed by solid tumors do not efficiently stimulate naive or activated T cells: implications for immunotherapy. J. Exp. Med. 186, 645-653 (1997).
56. Ochsenbein, A. F. et al. Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction. Nature 411, 1058-1064 (2001).
57. Marincola, F. M., Jaffee, E. M., Hicklin, D. J. & Ferrons, S. Escape of human solid tumors from T-cell recognition: molecular mechanisms and functional significance. Adv. Immunol. 74, 181-273 (2000).
58. Dunbar, P. R. et al. Cutting edge: rapid cloning of tumour-specific CTL suitable for adoptive immunotherapy of melanoma. J. Immunol. 162, 6959-6962 (1999).
59. + T cells in a large proportion of human histocompatibility leukocyte antigen (HLA)-A2 individuals. J. Exp. Med. 190, 705-715 (1999).
60. Speiser, D. E. et al. In vivo expression of natural killer cell inhibitory receptors by human melanoma-specific cytolytic T lymphocytes. J. Exp. Med. 190, 775-782 (1999).
61. + lymphocytes as compared with nonprofessional APC. J. Immunol. 167, 1188-1197 (2001).
62. Yee, C. et al. Melanocyte destruction after antigen-specific immunotherapy of melanoma: direct evidence of T-cell-mediated vitiligo. J. Exp. Med. 192, 1637-1644 (2000).
63. Ogg, G. S., Rod Dunbar, P. Romero, P., Chen, J. L. & Cerundolo, V. High frequency of skin-homing melanocyte-specific cytotoxic T lymphocytes in autoimmune vitiligo. J. Exp. Med. 188, 1203-1208 (1998).
64. Palermo, B. et al. Specific cytotoxic T-lymphocyte responses against Melan-A/MART1, tyrosinase and gp100 in vitiligo by the use of major histocompatibility complex/peptide tetramers: the role of cellular immunity in the etiopathogenesis of vitiligo. J. Invest. Dermatol. 117, 326-332 (2001).
65. - T lymphocytes detected in vitiligo patients are related to disease activity and are predominantly directed against MelanA/MART1. J. Invest. Dermatol. 116, 891-897 (2001).
66. Albert, M. L. et al. Tumor-specific killer cells in paraneoplastic cerebellar degeneration. Nature Med. 4, 1321-1324 (1998).
67. Jager, E. et al. Clonal expansion of Melan-A-specific cytotoxic T lymphocytes in a melanoma patient responding to continued immunization with melanoma-associated peptides. Int. J. Cancer 86, 538-547 (2000).
68. Mackensen, A. et al. Phase I study in melanoma patients of a vaccine with peptide-pulsed dendritic cells generated in vitro from CD34(+) hematopoietic progenitor cells. Int. J. Cancer 86, 385-392 (2000).
69. Marchand, M. et al. Tumor regressions observed in patients with metastatic melanoma treated with an antigenic peptide encoded by gene MAGE-3 and presented by HLA-A1. Int. J. Cancer 80, 219-230 (1999).
70. Rosenberg, S. A. et al. Immunologie and therapeutic evaluation of a synthetic peptide vaccine for the treatment of patients with metastatic melanoma. Nature Med. 4, 321-327 (1998).
71. Rosenberg, S. A. et al. Impact of cytokine administration on the generation of antitumor reactivity in patients with metastatic melanoma receiving a peptide vaccine. J. Immunol. 163, 1690-1695 (1999).
72. Scheibenbogen, C. et al. Phase II trial of vaccination with tyrosinase peptides and granulocyte-macrophage colony-stimulating factor in patients with metastatic melanoma. J. Immunother. 23, 275-281 (2000).
73. Nestle, F. O. et al. Vaccination of melanoma patients with peptide- or tumor-lysate-pulsed dendritic cells. Nature Med. 4, 328-33 (1998).
74. Dhodapkar, M. V. et al. Rapid generation of broad T-cell immunity in humans after a single injection of mature dendritic cells. J. Clin. Invest. 104, 173-180 (1999).
75. Schuler-Thurner, B. et al. MAGE-3 and influenza-matrix peptide-specific cytotoxic T cells are inducible in terminal stage HLA-A2.1* melanoma patients by mature monocyte-derived dendritic cells. J. Immunol. 165, 3492-3496 (2000).
76. + T cells. J. Immunol. 165, 2287-2296 (2000).
77. Lee, K. H. et al. Increased vaccine-specific T-cell frequency after peptide-based vaccination correlates with increased susceptibility to in vitro stimulation but does not lead to tumor regression. J. Immunol. 163, 6292-6300 (1999).
78. + T cells after vaccination with antigenic peptide. Clin. Cancer Res. 7, S796-S803 (2001).
79. Hanke, T. et al. Effective induction of simian-immunodeficiency-virus-specific cytotoxic T lymphocytes in macaques by using a multiepitope gene and DNA prime-modified vaccinia virus Ankara boost vaccination regimen. J. Virol. 73, 7524-7532 (1999).
80. Crawford, F. Konzono, H., White, J., Marrack, P. & Kappler, J. Detection of antigen-specific T cells with multivalent soluble class II MHC covalent peptide complexes. Immunity 8, 675-682 (1998).
81. Matsuda, J. et al. Tracking the response of natural killer T cells to a glycolipid antigen using CD1d tetramers. J. Exp. Med. 192, 741-754 (2000).
82. Benlagha, K., Weiss, A., Beavis, A., Teyton, L. & Bendelac, A. In vivo identification of glycolipid antigen-specific T cells using fluorescent CD1d tetramers. J. Exp. Med. 191, 1895-1903 (2000). The first paper to describe the use of tetramers specific for mouse NKT cells. These cross-react with human NKT cells and vice versa.
83. + memory. Nature Med. 7, 913-919 (2001). The first use of CD4 tetramers in an infection, which provides data on the dynamics of antiviral responses.
84. + T-cell responses during chronic virus infection. J. Exp. Med. 193, 297-305 (2001).
85. Kwok, W. W. et al. HLA-DQ tetramers identify epitope-specific T cells in peripheral blood of herpes simplex virus type-2-infected individuals: direct detection of immunodominant antigen-responsive cells. J. Immunol. 164, 4244-4249 (2000).
86. Meyer, A. et al. Direct enumeration of Borrelia-reactive CD4 T cells ex vivo using MHC class II tetramers. Proc. Natl Acad. Sci. 97, 11433-11438 (2000).
87. + T cells proliferating in response to influenza A antigen. J. Clin. Invest. 104, R63-R67 (1999).
88. + T cells by HLA-DR1 oligomers is dependent on the T-cell activation state. J. Immunol. 166, 741-746 (2001).
89. Karadimitris, A. et al. Human CD1d-glycolipid tetramers generated by in vitro oxidative refolding chromatography. Proc. Natl Acad. Sci. USA 96, 3294-3298 (2001).
90. + T lymphocytes. J. Immunol. (in the press).
91. Zinkernagel, R. M. Immunology taught by viruses. Science 271, 173-178 (1996).
92. Rosenberg, E. S. et al. Immune control of HIV-1 after early treatment of acute infection. Nature 407, 523-526 (2000). Successful therapy for HIV revealed by new techniques in T-cell immunology.
93. + T lymphocytes. Proc. Natl Acad. Sci. USA 97, 3382-3387 (2000).
94. + T cells. J. Immunol. 166, 7009-7013 (2001).
95. Denkberg, G., Cohen, C. J. & Reiter, Y. Critical role for CD8 in binding of MHC tetramers to TCR: CD8 antibodies block specific binding of human tumor-specific MHC-peptide tetramers to TCR. J. Immunol. 167, 270-276 (2001).
96. Whelan, J. A. et al. Specificity of CTL interactions with peptide-MHC class I tetrameric complexes is temperature dependent. J. Immunol. 163, 4342-4348 (1999).
97. Skinner, P., Daniels, M., Schmidt, C., Jameson, S. & Hasse, A. In situ tetramer staining of antigen-specific T cells in tissues. J. Immunol. 165, 613-617 (2000).
98. Rubio-Godoy, V. et al. Discrepancy between ELISPOT IFN-γ secretion and binding of A2/peptide multimers to TCR reveals interclonal dissociation of CTL effector function from TCR-peptide/MHC complexes half-life. Proc. Natl Acad. Sci. USA 98, 10302-10307 (2001).
99. + memory T cells. J. Exp. Med. 186, 859-865 (1997).
100. + T cells produce antiviral cytokines but are impaired in cytolytic function. J. Exp. Med. 192, 63-75 (2000).
101. Goulder, P. J. et al. Functionally inert HIV-specific cytotoxic T lymphocytes do not play a major role in chronically infected adults and children. J. Exp. Med. 192, 1819-1832 (2000). Comprehensive analysis of tetramer staining versus functional staining in HIV. Other authors have described greater differences between the two.
102. + T-cell memory in vivo. Eur. J. Immunol. 28, 4382-4390 (1998).
103. Ciurea, A. et al. Persistence of lymphocytic choriomeningitis virus at very low levels in immune mice. Proc. Natl Acad. Sci. USA 96, 11964-11989 (1999).
104. Price, G. E., Ou, R., Jiang, H., Huang, L. & Moskophidis, D. Viral escape by selection of cytotoxic T-cell-resistant variants in influenza A virus pneumonia. J. Exp. Med. 191, 1853-1867 (2000).
105. + T-cell proliferation in the acute and persistent phases of a γ-herpesvirus infection. J. Virol. 75, 4435-4438 (2001).
106. Busch, D., Pilip, I., Vijh, S. & Pamer, E. Coordinate regulation of complex T-cell populations responding to bacterial infection. Immunity 8, 353-362 (1998).
107. + T cells with soluble HLA-A2/Tax11-19 tetramer complexes in patients with humen T-cell lymphotropic virus-associated myelopathy. J. Immunol. 162, 1765-1771 (1999).
108. + cytotoxic lymphocyte responses against cytomegalovirus after liver transplantation: correlation with time from transplant to receipt of tacrolimus. J. Infect. Dis. 183, 835-843 (2001).
109. + T lymphocytes using MHC tetramers in kidney transplant patients and healthy participants. Transplantation 69, 2243-2250 (2000).