Can Non-lytic CD8+ T Cells Drive HIV-1 Escape?

PLoS Pathogens

Volumn 9, Issue 11, 2013, Pages

  Seich al Basatena, Nafisa Katrin ^a   Chatzimichalis, Konstantinos ^b   Graw, Frederik ^c,d   Frost, Simon D W ^e   Regoes, Roland R ^f   Asquith, Becca ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF LONDON   (United Kingdom)

^c LOS ALAMOS NATIONAL LABORATORY   (United States)

^d UNIVERSITY OF HEIDELBERG   (Germany)

^e UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^f ETH ZURICH   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

EPITOPE;

ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL DEATH; CELL MOTILITY; CELL POPULATION; CELL PROLIFERATION; CELL SIZE; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFECTION CONTROL; PREDICTION; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; SIMULATION; SPLEEN CELL; THEORETICAL MODEL; VIREMIA; VIRUS REPLICATION;

CD8-POSITIVE T-LYMPHOCYTES; HIV INFECTIONS; HIV-1; HUMANS; IMMUNE EVASION; MODELS, IMMUNOLOGICAL;

EID: 84888250385     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1003656     Document Type: Article

References (111)

1. Schmitz JE, Kuroda MJ, Santra S, Sasseville VG, Simon MA, et al. (1999) Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science (New York, NY) 283: 857-860.
2. Wiviott LD, Walker CM, Levy JA, (1990) CD8+ lymphocytes suppress HIV production by autologous CD4+ cells without eliminating the infected cells from culture. Cell Immunol 128: 628-634.
3. Yang OO, Kalams SA, Trocha A, Cao H, Luster A, et al. (1997) Suppression of human immunodeficiency virus type 1 replication by CD8+ cells: evidence for HLA class I-restricted triggering of cytolytic and noncytolytic mechanisms. Journal of Virology 71: 3120-3128.
4. Geiben-Lynn R, (2002) Anti-human immunodeficiency virus noncytolytic CD8+ T-cell response: a review. AIDS Patient Care and STDs 16: 471-477.
5. DeVico AL, Gallo RC, (2004) Control of HIV-1 infection by soluble factors of the immune response. Nature Reviews Microbiology 2: 401-413.
6. Walker CM, Erickson AL, Hsueh FC, Levy JA, (1991) Inhibition of human immunodeficiency virus replication in acutely infected CD4+ cells by CD8+ cells involves a noncytotoxic mechanism. J Virol 65: 5921-5927.
7. Walker CM, Levy JA, (1989) A diffusible lymphokine produced by CD8+ T lymphocytes suppresses HIV replication. Immunology 66: 628-630.
8. Levy JA, Mackewicz CE, Barker E, (1996) Controlling HIV pathogenesis: the role of the noncytotoxic anti-HIV response of CD8+ T cells. Immunol Today 17: 217-224.
9. Walker CM, Moody DJ, Stites DP, Levy JA, (1986) CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science 234: 1563-1566.
10. Hammer SM, Gillis JM, Groopman JE, Rose RM, (1986) In vitro modification of human immunodeficiency virus infection by granulocyte-macrophage colony-stimulating factor and gamma interferon. Proc Natl Acad Sci U S A 83: 8734-8738.
11. Nakashima H, Yoshida T, Harada S, Yamamoto N, (1986) Recombinant human interferon gamma suppresses HTLV-III replication in vitro. Int J Cancer 38: 433-436.
12. Wong GH, Krowka JF, Stites DP, Goeddel DV, (1988) In vitro anti-human immunodeficiency virus activities of tumor necrosis factor-alpha and interferon-gamma. J Immunol 140: 120-124.
13. Agy MB, Acker RL, Sherbert CH, Katze MG, (1995) Interferon Treatment Inhibits Virus Replication in HIV-1- and SIV-Infected CD4+ T-Cell Lines by Distinct Mechanisms: Evidence for Decreased Stability and Aberrant Processing of HIV-1 Proteins. Virology 214: 379-386.
14. Koyanagi Y, O'Brien WA, Zhao JQ, Golde DW, Gasson JC, et al. (1988) Cytokines alter production of HIV-1 from primary mononuclear phagocytes. Science 241: 1673-1675.
15. Yamada O, Hattori N, Kurimura T, Kita M, Kishida T, (1988) Inhibition of growth of HIV by human natural interferon in vitro. AIDS Res Hum Retroviruses 4: 287-294.
16. Yamamoto JK, Barre-Sinoussi F, Bolton V, Pedersen NC, Gardner MB, (1986) Human alpha- and beta-interferon but not gamma- suppress the in vitro replication of LAV, HTLV-III, and ARV-2. J Interferon Res 6: 143-152.
17. Brinchmann JE, Gaudernack G, Vartdal F, (1991) In vitro replication of HIV-1 in naturally infected CD4+ T cells is inhibited by rIFN alpha 2 and by a soluble factor secreted by activated CD8+ T cells, but not by rIFN beta, rIFN gamma, or recombinant tumor necrosis factor-alpha. J Acquir Immune Defic Syndr 4: 480-488.
18. Cocchi F, DeVico AL, Garzino-Demo A, Arya SK, Gallo RC, et al. (1995) Identification of RANTES, MIP-1 alpha, and MIP-1 beta as the major HIV-suppressive factors produced by CD8+ T cells. Science (New York, NY) 270: 1811-1815.
19. Garzino-Demo A, DeVico AL, Conant KE, Gallo RC, (2000) The role of chemokines in human immunodeficiency virus infection. Immunol Rev 177: 79-87.
20. Liu H, Chao D, Nakayama EE, Taguchi H, Goto M, et al. (1999) Polymorphism in RANTES chemokine promoter affects HIV-1 disease progression. Proc Natl Acad Sci U S A 96: 4581-4585.
21. Mackewicz CE, Barker E, Greco G, Reyes-Teran G, Levy JA, (1997) Do beta-chemokines have clinical relevance in HIV infection? J Clin Invest 100: 921-930.
22. Saha K, Bentsman G, Chess L, Volsky DJ, (1998) Endogenous production of beta-chemokines by CD4+, but not CD8+, T-cell clones correlates with the clinical state of human immunodeficiency virus type 1 (HIV-1)-infected individuals and may be responsible for blocking infection with non-syncytium-inducing HIV-1 in vitro. J Virol 72: 876-881.
23. Chen CH, Weinhold KJ, Bartlett JA, Bolognesi DP, Greenberg ML, (1993) CD8+ T lymphocyte-mediated inhibition of HIV-1 long terminal repeat transcription: a novel antiviral mechanism. AIDS Res Hum Retroviruses 9: 1079-1086.
24. Copeland KF, McKay PJ, Rosenthal KL, (1995) Suppression of activation of the human immunodeficiency virus long terminal repeat by CD8+ T cells is not lentivirus specific. AIDS Res Hum Retroviruses 11: 1321-1326.
25. Mackewicz CE, Blackbourn DJ, Levy JA, (1995) CD8+ T cells suppress human immunodeficiency virus replication by inhibiting viral transcription. Proc Natl Acad Sci U S A 92: 2308-2312.
26. Klatt NR, Shudo E, Ortiz AM, Engram JC, Paiardini M, et al. (2010) CD8+ Lymphocytes Control Viral Replication in SIVmac239-Infected Rhesus Macaques without Decreasing the Lifespan of Productively Infected Cells. PLoS Pathog 6: e1000747-e1000747.
27. Wong JK, Strain MC, Porrata R, Reay E, Sankaran-Walters S, et al. (2010) In Vivo CD8+ T-Cell Suppression of SIV Viremia Is Not Mediated by CTL Clearance of Productively Infected Cells. PLoS Pathog 6: e1000748-e1000748.
28. Elemans M, Seich Al Basatena N-K, Klatt NR, Gkekas C, Silvestri G, et al. (2011) Why Don't CD8+ T Cells Reduce the Lifespan of SIV-Infected Cells In Vivo? PLoS Computational Biology 7: e1002200-e1002200.
29. Wick WD, Yang OO, (2012) Biologically-Directed Modeling Reflects Cytolytic Clearance of SIV-Infected Cells In Vivo in Macaques. PLoS ONE 7 (9):: e44778 doi:10.1371/journal.pone.0044778.
30. Klenerman P, Phillips RE, Rinaldo CR, Wahl LM, Ogg G, et al. (1996) Cytotoxic T lymphocytes and viral turnover in HIV type 1 infection. Proceedings of the National Academy of Sciences of the United States of America 93: 15323-15328.
31. Almeida JR, Price DA, Papagno L, Arkoub ZA, Sauce D, et al. (2007) Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. The Journal of Experimental Medicine 204: 2473-2485.
32. Coffin JM, (1995) HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 267: 483-489.
33. Borrow P, Lewicki H, Wei X, Horwitz MS, Peffer N, et al. (1997) Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nature Medicine 3: 205-211.
34. Price DA, Goulder PJ, Klenerman P, Sewell AK, Easterbrook PJ, et al. (1997) Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection. Proceedings of the National Academy of Sciences of the United States of America 94: 1890-1895.
35. Jones NA, Wei X, Flower DR, Wong M, Michor F, et al. (2004) Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response. The Journal of Experimental Medicine 200: 1243-1256.
36. Mudd PA, Ericsen AJ, Burwitz BJ, Wilson NA, O'Connor DH, et al. (2012) Escape from CD8(+) T cell responses in Mamu-B*00801(+) macaques differentiates progressors from elite controllers. Journal of Immunology (Baltimore, Md: 1950) 188: 3364-3370.
37. Jamieson BD, Yang OO, Hultin L, Hausner MA, Hultin P, et al. (2003) Epitope Escape Mutation and Decay of Human Immunodeficiency Virus Type 1-Specific CTL Responses. The Journal of Immunology 171: 5372-5379.
38. Phillips RE, Rowland-Jones S, Nixon DF, Gotch FM, Edwards JP, et al. (1991) Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature 354: 453-459.
39. Geels MJ, Cornelissen M, Schuitemaker H, Anderson K, Kwa D, et al. (2003) Identification of sequential viral escape mutants associated with altered T-cell responses in a human immunodeficiency virus type 1-infected individual. Journal of Virology 77: 12430-12440.
40. Koenig S, Conley AJ, Brewah YA, Jones GM, Leath S, et al. (1995) Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression. Nature Medicine 1: 330-336.
41. Mempel TR, Pittet MJ, Khazaie K, Weninger W, Weissleder R, et al. (2006) Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation. Immunity 25: 129-141.
42. Wiedemann A, Depoil D, Faroudi M, Valitutti S, (2006) Cytotoxic T lymphocytes kill multiple targets simultaneously via spatiotemporal uncoupling of lytic and stimulatory synapses. Proceedings of the National Academy of Sciences of the United States of America 103: 10985-10990.
43. Miller MJ, Wei SH, Parker I, Cahalan MD, (2002) Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science (New York, NY) 296: 1869-1873.
44. Muller AJ, Filipe-Santos O, Eberl G, Aebischer T, Spath GF, et al. (2012) CD4+ T cells rely on a cytokine gradient to control intracellular pathogens beyond sites of antigen presentation. Immunity 37: 147-157.
45. Goonetilleke N, Liu MK, Salazar-Gonzalez JF, Ferrari G, Giorgi E, et al. (2009) The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J Exp Med 206: 1253-1272.
46. Mandl JN, Regoes RR, Garber DA, Feinberg MB, (2007) Estimating the effectiveness of simian immunodeficiency virus-specific CD8+ T cells from the dynamics of viral immune escape. J Virol 81: 11982-11991.
47. Ganusov VV, Goonetilleke N, Liu MK, Ferrari G, Shaw GM, et al. (2011) Fitness costs and diversity of CTL response determine the rate of CTL escape during the acute and chronic phases of HIV infection. J Virol 85: 10518-10528.
48. Asquith B, McLean AR, (2007) In Vivo CD8+ T Cell Control of Immunodeficiency Virus Infection in Humans and Macaques. Proceedings of the National Academy of Sciences 104: 6365-6370.
49. Asquith B, Edwards CT, Lipsitch M, McLean AR, (2006) Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. PLoS Biology 4: e90.
50. Fischer W, Ganusov VV, Giorgi EE, Hraber PT, Keele BF, et al. Transmission of Single HIV-1 Genomes and Dynamics of Early Immune Escape Revealed by Ultra-Deep Sequencing. PLoS ONE 5: e12303.
51. Beltman JB, Marée AFM, de Boer RJ, (2007) Spatial modelling of brief and long interactions between T cells and dendritic cells. Immunology and Cell Biology 85: 306-314.
52. Beltman JB, Marée AFM, Lynch JN, Miller MJ, de Boer RJ, (2007) Lymph node topology dictates T cell migration behavior. The Journal of Experimental Medicine 204: 771-780.
53. Graw F, Regoes RR, (2009) Investigating CTL Mediated Killing with a 3D Cellular Automaton. PLoS Comput Biol 5.
54. Bauer AL, Beauchemin CAA, Perelson AS, (2009) Agent-based modeling of host-pathogen systems: The successes and challenges. Information Sciences 179: 1379-1389.
55. Mempel TR, Pittet MJ, Khazaie K, Weninger W, Weissleder R, et al. (2006) Regulatory T cells reversibly suppress cytotoxic T cell function independent of effector differentiation. Immunity 25: 129-141.
56. Egen Jackson G, Rothfuchs Antonio G, Feng Carl G, Horwitz Marcus A, Sher A, et al. (2011) Intravital Imaging Reveals Limited Antigen Presentation and T Cell Effector Function in Mycobacterial Granulomas. Immunity 34: 807-819.
57. Miller MJ, Safrina O, Parker I, Cahalan MD, (2004) Imaging the single cell dynamics of CD4+ T cell activation by dendritic cells in lymph nodes. The Journal of Experimental Medicine 200: 847-856.
58. Miller MJ, Wei SH, Cahalan MD, Parker I, (2003) Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy. Proceedings of the National Academy of Sciences of the United States of America 100: 2604-2609.
59. Boissonnas A, Fetler L, Zeelenberg IS, Hugues S, Amigorena S, (2007) In vivo imaging of cytotoxic T cell infiltration and elimination of a solid tumor. The Journal of Experimental Medicine 204: 345-356.
60. Worbs T, Mempel TR, Bölter J, von Andrian UH, Förster R, (2007) CCR7 ligands stimulate the intranodal motility of T lymphocytes in vivo. The Journal of Experimental Medicine 204: 489-495.
61. Aoshi T, Zinselmeyer BH, Konjufca V, Lynch JN, Zhang X, et al. (2008) Bacterial entry to the splenic white pulp initiates antigen presentation to CD8+ T cells. Immunity 29: 476-486.
62. Bajénoff M, Glaichenhaus N, Germain RN, (2008) Fibroblastic reticular cells guide T lymphocyte entry into and migration within the splenic T cell zone. Journal of Immunology (Baltimore, Md: 1950) 181: 3947-3954.
63. Little SJ, McLean AR, Spina CA, Richman DD, Havlir DV, (1999) Viral dynamics of acute HIV-1 infection. The Journal of Experimental Medicine 190: 841-850.
64. Nowak MA, Lloyd AL, Vasquez GM, Wiltrout TA, Wahl LM, et al. (1997) Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection. Journal of Virology 71: 7518-7525.
65. Ribeiro RM, Qin L, Chavez LL, Li D, Self SG, et al. (2010) Estimation of the initial viral growth rate and basic reproductive number during acute HIV-1 infection. Journal of Virology 84: 6096-6102.
66. Haase AT, (1999) Population biology of HIV-1 infection: viral and CD4+ T cell demographics and dynamics in lymphatic tissues. Annual Review of Immunology 17: 625-656.
67. Signoret N, Pelchen-Matthews A, Mack M, Proudfoot AE, Marsh M, (2000) Endocytosis and recycling of the HIV coreceptor CCR5. The Journal of Cell Biology 151: 1281-1294.
68. Milicic A, Edwards CTT, Hué S, Fox J, Brown H, et al. (2005) Sexual transmission of single human immunodeficiency virus type 1 virions encoding highly polymorphic multisite cytotoxic T-lymphocyte escape variants. Journal of Virology 79: 13953-13962.
69. Sanderson NSR, Puntel M, Kroeger KM, Bondale NS, Swerdlow M, et al. (2012) Cytotoxic immunological synapses do not restrict the action of interferon-γ to antigenic target cells. Proceedings of the National Academy of Sciences of the United States of America 10.1073/pnas.1116058109.
70. Goulder PJ, Phillips RE, Colbert RA, McAdam S, Ogg G, et al. (1997) Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nature Medicine 3: 212-217.
71. Barouch DH, (2008) Challenges in the Development of an HIV-1 Vaccine. Nature 455: 613-619.
72. Feeney ME, Tang Y, Pfafferott K, Roosevelt KA, Draenert R, et al. (2005) HIV-1 viral escape in infancy followed by emergence of a variant-specific CTL response. Journal of Immunology (Baltimore, Md: 1950) 174: 7524-7530.
73. Saunders KO, Ward-Caviness C, Schutte RJ, Freel SA, Overman RG, et al. (2011) Secretion of MIP-1β and MIP-1α by CD8(+) T-lymphocytes correlates with HIV-1 inhibition independent of coreceptor usage. Cellular Immunology 266: 154-164.
74. Kadolsky UD, Asquith B, (2010) Quantifying the Impact of Human Immunodeficiency Virus-1 Escape From Cytotoxic T-Lymphocytes. PLoS Comput Biol 6: e1000981-e1000981.
75. Hay CM, Ruhl DJ, Basgoz NO, Wilson CC, Billingsley JM, et al. (1999) Lack of viral escape and defective in vivo activation of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes in rapidly progressive infection. Journal of Virology 73: 5509-5519.
76. Graw F, Regoes RR, (2012) Influence of the fibroblastic reticular network on cell-cell interactions in lymphoid organs. PLoS Computational Biology 8: e1002436-e1002436.
77. Mostowy R, Kouyos RD, Hoof I, Hinkley T, Haddad M, et al. (2012) Estimating the fitness cost of escape from HLA presentation in HIV-1 protease and reverse transcriptase. PLoS Computational Biology 8(5): e1002525 doi:10.1371/journal.pcbi.1002525.
78. Jung A, Maier R, Vartanian J-P, Bocharov G, Jung V, et al. (2002) Recombination: Multiply infected spleen cells in HIV patients. Nature 418: 144-144.
79. Josefsson L, King MS, Makitalo B, Brännström J, Shao W, et al. (2011) Majority of CD4+ T cells from peripheral blood of HIV-1-infected individuals contain only one HIV DNA molecule. Proceedings of the National Academy of Sciences of the United States of America 108: 11199-11204.
80. Mohri H, Perelson AS, Tung K, Ribeiro RM, Ramratnam B, et al. (2001) Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. The Journal of Experimental Medicine 194: 1277-1287.
81. Bogle G, Dunbar PR, (2008) Simulating T-cell motility in the lymph node paracortex with a packed lattice geometry. Immunology and Cell Biology 86: 676-687.
82. Stafford MA, Corey L, Cao Y, Daar ES, Ho DD, et al. (2000) Modeling plasma virus concentration during primary HIV infection. Journal of Theoretical Biology 203: 285-301.
83. Strain MC, Richman DD, Wong JK, Levine H, (2002) Spatiotemporal dynamics of HIV propagation. J Theor Biol 218: 85-96.
84. Schacker T, Little S, Connick E, Gebhard K, Zhang ZQ, et al. (2001) Productive infection of T cells in lymphoid tissues during primary and early human immunodeficiency virus infection. J Infect Dis 183: 555-562.
85. Frost SD, Dumaurier MJ, Wain-Hobson S, Brown AJ, (2001) Genetic drift and within-host metapopulation dynamics of HIV-1 infection. Proc Natl Acad Sci U S A 98: 6975-6980.
86. McKeating J, Balfe P, Clapham P, Weiss RA, (1991) Recombinant CD4-selected human immunodeficiency virus type 1 variants with reduced gp120 affinity for CD4 and increased cell fusion capacity. J Virol 65: 4777-4785.
87. McKeating JA, McKnight A, Moore JP, (1991) Differential loss of envelope glycoprotein gp120 from virions of human immunodeficiency virus type 1 isolates: effects on infectivity and neutralization. J Virol 65: 852-860.
88. Zhang L, Dailey PJ, He T, Gettie A, Bonhoeffer S, et al. (1999) Rapid clearance of simian immunodeficiency virus particles from plasma of rhesus macaques. J Virol 73: 855-860.
89. Ramratnam B, Bonhoeffer S, Binley J, Hurley A, Zhang L, et al. (1999) Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis. Lancet 354: 1782-1785.
90. Jolly C, Kashefi K, Hollinshead M, Sattentau QJ, (2004) HIV-1 cell to cell transfer across an Env-induced, actin-dependent synapse. J Exp Med 199: 283-293.
91. Rudnicka D, Feldmann J, Porrot F, Wietgrefe S, Guadagnini S, et al. (2009) Simultaneous cell-to-cell transmission of human immunodeficiency virus to multiple targets through polysynapses. J Virol 83: 6234-6246.
92. Sourisseau M, Sol-Foulon N, Porrot F, Blanchet F, Schwartz O, (2007) Inefficient human immunodeficiency virus replication in mobile lymphocytes. J Virol 81: 1000-1012.
93. Hubner W, McNerney GP, Chen P, Dale BM, Gordon RE, et al. (2009) Quantitative 3D video microscopy of HIV transfer across T cell virological synapses. Science 323: 1743-1747.
94. Mazurov D, Ilinskaya A, Heidecker G, Lloyd P, Derse D, (2010) Quantitative comparison of HTLV-1 and HIV-1 cell-to-cell infection with new replication dependent vectors. PLoS Pathog 6: e1000788.
95. Asquith B, Debacq C, Macallan DC, Willems L, Bangham CRM, (2002) Lymphocyte kinetics: the interpretation of labelling data. Trends in Immunology 23: 596-601.
96. Dixit NM, Markowitz M, Ho DD, Perelson AS, (2004) Estimates of intracellular delay and average drug efficacy from viral load data of HIV-infected individuals under antiretroviral therapy. Antiviral Therapy 9: 237-246.
97. Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD, (1996) HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science (New York, NY) 271: 1582-1586.
98. Markowitz M, Louie M, Hurley A, Sun E, Di Mascio M, et al. (2003) A novel antiviral intervention results in more accurate assessment of human immunodeficiency virus type 1 replication dynamics and T-cell decay in vivo. Journal of Virology 77: 5037-5038.
99. Zheng H, Jin B, Henrickson SE, Perelson AS, von Andrian UH, et al. (2008) How antigen quantity and quality determine T-cell decisions in lymphoid tissue. Molecular and Cellular Biology 28: 4040-4051.
100. Perelson AS, Macken CA, Grimm EA, Roos LS, Bonavida B, (1984) Mechanism of cell-mediated cytotoxicity at the single cell level. VIII. Kinetics of lysis of target cells bound by more than one cytotoxic T lymphocyte. Journal of Immunology (Baltimore, Md: 1950) 132: 2190-2198.
101. Zagury D, Bernard J, Jeannesson P, Thiernesse N, Cerottini JC, (1979) Studies on the mechanism of T cell-mediated lysis at the single effector cell level. I. Kinetic analysis of lethal hits and target cell lysis in multicellular conjugates. Journal of Immunology (Baltimore, Md: 1950) 123: 1604-1609.
102. Stinchcombe JC, Griffiths GM, (2007) Secretory mechanisms in cell-mediated cytotoxicity. Annual Review of Cell and Developmental Biology 23: 495-517.
103. Dushek O, Aleksic M, Wheeler RJ, Zhang H, Cordoba S-P, et al. (2011) Antigen potency and maximal efficacy reveal a mechanism of efficient T cell activation. Science Signaling 4: ra39-ra39.
104. González PA, Carreño LJ, Coombs D, Mora JE, Palmieri E, et al. (2005) T Cell Receptor Binding Kinetics Required for T Cell Activation Depend on the Density of Cognate Ligand on the Antigen-Presenting Cell. Proceedings of the National Academy of Sciences of the United States of America 102: 4824-4829.
105. Krogsgaard M, Prado N, Adams EJ, He X-l, Chow D-C, et al. (2003) Evidence that structural rearrangements and/or flexibility during TCR binding can contribute to T cell activation. Molecular Cell 12: 1367-1378.
106. Aleksic M, Dushek O, Zhang H, Shenderov E, Chen J-L, et al. (2010) Dependence of T Cell Antigen Recognition on T Cell Receptor-Peptide MHC Confinement Time. Immunity 32: 163-174.
107. Chervin AS, Stone JD, Holler PD, Bai A, Chen J, et al. (2009) The Impact of TCR-Binding Properties and Antigen Presentation Format on T Cell Responsiveness. The Journal of Immunology 183: 1166-1178.
108. Regoes RR, Yates A, Antia R, (2007) Mathematical models of cytotoxic T-lymphocyte killing. Immunology and Cell Biology 85: 274-279.
109. Isaaz S, Baetz K, Olsen K, Podack E, Griffiths GM, (1995) Serial killing by cytotoxic T lymphocytes: T cell receptor triggers degranulation, re-filling of the lytic granules and secretion of lytic proteins via a non-granule pathway. European Journal of Immunology 25: 1071-1079.
110. Pores-Fernando AT, Bauer RA, Wurth GA, Zweifach A, (2005) Exocytic responses of single leukaemic human cytotoxic T lymphocytes stimulated by agents that bypass the T cell receptor. The Journal of Physiology 567: 891-903.
111. Slifka MK, Rodriguez F, Whitton JL, (1999) Rapid on/off cycling of cytokine production by virus-specific CD8+ T cells. Nature 401: 76-79.