HIV-1-specific CD8 T cells exhibit limited cross-reactivity during acute infection

Journal of Immunology

Volumn 196, Issue 8, 2016, Pages 3276-3286

  Du, Victor Y ^a   Bansal, Anju ^a   Carlson, Jonathan ^b   Salazar Gonzalez, Jesus F ^a   Salazar, Maria G ^a   Ladell, Kristin ^c   Gras, Stephanie ^d   Josephs, Tracy M ^d   Heath, Sonya L ^a   Price, David A ^c,e   Rossjohn, Jamie ^c,d   Hunter, Eric ^f   Goepfert, Paul A ^a  

^a University of Alabama at Birmingham   (United States)

^b MICROSOFT RESEARCH   (United States)

^c CARDIFF UNIVERSITY SCHOOL OF MEDICINE   (United Kingdom)

^d MONASH UNIVERSITY   (Australia)

^e NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^f EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPITOPE; HLA ANTIGEN CLASS 1; T LYMPHOCYTE RECEPTOR; HLA B27 ANTIGEN; HLA B7 ANTIGEN; HLA-B*07:02 ANTIGEN; HLA-B*27:05 ANTIGEN;

AMINO ACID SEQUENCE; ANTIGEN RECOGNITION; ARTICLE; CD8+ T LYMPHOCYTE; CLINICAL ARTICLE; CONTROLLED STUDY; CROSS REACTION; CYTOTOXICITY ASSAY; GENE SEQUENCE; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; IN VIVO STUDY; NONHUMAN; PRIORITY JOURNAL; PROTEIN STRUCTURE; VIRUS TRANSMISSION; CELL LINE; CLASSIFICATION; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; ULTRASTRUCTURE; VIROLOGY; X RAY CRYSTALLOGRAPHY;

CD8-POSITIVE T-LYMPHOCYTES; CELL LINE; CROSS REACTIONS; CRYSTALLOGRAPHY, X-RAY; EPITOPES, T-LYMPHOCYTE; HIV INFECTIONS; HIV-1; HLA-B27 ANTIGEN; HLA-B7 ANTIGEN; HUMANS;

EID: 84974802815     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1502411     Document Type: Article

References (75)

1. Gulick, R. M., J. W. Mellors, D. Havlir, J. J. Eron, C. Gonzalez, D. McMahon, D. D. Richman, F. T. Valentine, L. Jonas, A. Meibohm, et al. 1997. Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy. N. Engl. J. Med. 337: 734-739.
2. Shah, M., K. Risher, S. A. Berry, and D. W. Dowdy. 2016. The epidemiologic and economic impact of improving HIV testing, linkage, and retention in care in the United States. Clin. Infect. Dis. 62: 220-229
3. Martin, M., S. Vanichseni, P. Suntharasamai, U. Sangkum, P. A. Mock, M. Leethochawalit, S. Chiamwongpaet, M. E. Curlin, S. Na-Pompet, A. Warapronmongkholkul, et al; Bangkok Tenofovir Study Group. 2015. The impact of adherence to preexposure prophylaxis on the risk of HIV infection among people who inject drugs. AIDS 29: 819-824.
4. Koup, R. A., J. T. Safrit, Y. Cao, C. A. Andrews, G. McLeod, W. Borkowsky, C. Farthing, and D. D. Ho. 1994. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J. Virol. 68: 4650-4655.
5. Leslie, A. J., K. J. Pfafferott, P. Chetty, R. Draenert, M. M. Addo, M. Feeney, Y. Tang, E. C. Holmes, T. Allen, J. G. Prado, et al. 2004. HIV evolution: CTL escape mutation and reversion after transmission. Nat. Med. 10: 282-289.
6. Schmitz, J. E., M. J. Kuroda, S. Santra, V. G. Sasseville, M. A. Simon, M. A. Lifton, P. Racz, K. Tenner-Racz, M. Dalesandro, B. J. Scallon, et al. 1999. Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283: 857-860.
7. Mudd, P. A., M. A. Martins, A. J. Ericsen, D. C. Tully, K. A. Power, A. T. Bean, S. M. Piaskowski, L. Duan, A. Seese, A. D. Gladden, et al. 2012. Vaccineinduced CD8+ T cells control AIDS virus replication. Nature 491: 129-133.
8. Goulder, P. J., and D. I. Watkins. 2008. Impact of MHC class I diversity on immune control of immunodeficiency virus replication. Nat. Rev. Immunol. 8: 619-630.
9. Buchbinder, S. P., D. V. Mehrotra, A. Duerr, D. W. Fitzgerald, R. Mogg, D. Li, P. B. Gilbert, J. R. Lama, M. Marmor, C. Del Rio, et al; Step Study Protocol Team. 2008. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-ofconcept trial. Lancet 372: 1881-1893.
10. Cohen, J. 2013. AIDS research. More woes for struggling HIV vaccine field. Science 340: 667.
11. McElrath, M. J., S. C. De Rosa, Z. Moodie, S. Dubey, L. Kierstead, H. Janes, O. D. Defawe, D. K. Carter, J. Hural, R. Akondy, et al; Step Study Protocol Team. 2008. HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet 372: 1894-1905.
12. Brumme, Z. L., M. John, J. M. Carlson, C. J. Brumme, D. Chan, M. A. Brockman, L. C. Swenson, I. Tao, S. Szeto, P. Rosato, et al. 2009. HLAassociated immune escape pathways in HIV-1 subtype B Gag, Pol and Nef proteins. PLoS One 4: e6687.
13. Carlson, J. M., C. J. Brumme, E. Martin, J. Listgarten, M. A. Brockman, A. Q. Le, C. K. Chui, L. A. Cotton, D. J. Knapp, S. A. Riddler, et al; International HIV Adaptation Collaborative. 2012. Correlates of protective cellular immunity revealed by analysis of population-level immune escape pathways in HIV-1. J. Virol. 86: 13202-13216.
14. Karlsson, A. C., A. K. Iversen, J. M. Chapman, T. de Oliviera, G. Spotts, A. J. McMichael, M. P. Davenport, F. M. Hecht, and D. F. Nixon. 2007. Sequential broadening of CTL responses in early HIV-1 infection is associated with viral escape. PLoS One 2: e225.
15. Price, D. A., P. J. Goulder, P. Klenerman, A. K. Sewell, P. J. Easterbrook, M. Troop, C. R. Bangham, and R. E. Phillips. 1997. Positive selection of HIV-1 cytotoxic T lymphocyte escape variants during primary infection. Proc. Natl. Acad. Sci. USA 94: 1890-1895.
16. Yokomaku, Y., H. Miura, H. Tomiyama, A. Kawana-Tachikawa, M. Takiguchi, A. Kojima, Y. Nagai, A. Iwamoto, Z. Matsuda, and K. Ariyoshi. 2004. Impaired processing and presentation of cytotoxic-T-lymphocyte (CTL) epitopes are major escape mechanisms from CTL immune pressure in human immunodeficiency virus type 1 infection. J. Virol. 78: 1324-1332.
17. Goulder, P. J., and D. I. Watkins. 2004. HIV and SIV CTL escape: implications for vaccine design. Nat. Rev. Immunol. 4: 630-640.
18. Goulder, P. J., R. E. Phillips, R. A. Colbert, S. McAdam, G. Ogg, M. A. Nowak, P. Giangrande, G. Luzzi, B. Morgan, A. Edwards, et al. 1997. Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat. Med. 3: 212-217.
19. Moore, C. B., M. John, I. R. James, F. T. Christiansen, C. S. Witt, and S. A. Mallal. 2002. Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science 296: 1439-1443.
20. Arstila, T. P., A. Casrouge, V. Baron, J. Even, J. Kanellopoulos, and P. Kourilsky. 1999. A direct estimate of the human ab T cell receptor diversity. Science 286: 958-961.
21. Mason, D. 1998. A very high level of crossreactivity is an essential feature of the T-cell receptor. Immunol. Today 19: 395-404.
22. Wooldridge, L., B. Laugel, J. Ekeruche, M. Clement, H. A. van den Berg, D. A. Price, and A. K. Sewell. 2010. CD8 controls T cell cross-reactivity. J. Immunol. 185: 4625-4632.
23. Chen, H., Z. M. Ndhlovu, D. Liu, L. C. Porter, J. W. Fang, S. Darko, M. A. Brockman, T. Miura, Z. L. Brumme, A. Schneidewind, et al. 2012. TCR clonotypes modulate the protective effect of HLA class I molecules in HIV-1 infection. Nat. Immunol. 13: 691-700.
24. Turnbull, E. L., A. R. Lopes, N. A. Jones, D. Cornforth, P. Newton, D. Aldam, P. Pellegrino, J. Turner, I. Williams, C. M. Wilson, et al. 2006. HIV-1 epitopespecific CD8+ T cell responses strongly associated with delayed disease progression cross-recognize epitope variants efficiently. J. Immunol. 176: 6130-6146.
25. Mothe, B., A. Llano, J. Ibarrondo, J. Zamarreño, M. Schiaulini, C. Miranda, M. Ruiz-Riol, C. T. Berger, M. J. Herrero, E. Palou, et al. 2012. CTL responses of high functional avidity and broad variant cross-reactivity are associated with HIV control. PLoS One 7: e29717.
26. Ladell, K., M. Hashimoto, M. C. Iglesias, P. G.Wilmann, J. E. McLaren, S. Gras, T. Chikata, N. Kuse, S. Fastenackels, E. Gostick, et al. 2013. A molecular basis for the control of preimmune escape variants by HIV-specific CD8+ T cells. Immunity 38: 425-436.
27. Schaubert, K. L., D. A. Price, J. R. Salkowitz, A. K. Sewell, J. Sidney, T. E. Asher, S. E. Blondelle, S. Adams, F. M. Marincola, A. Joseph, et al. 2010. Generation of robust CD8+ T-cell responses against subdominant epitopes in conserved regions of HIV-1 by repertoire mining with mimotopes. Eur. J. Immunol. 40: 1950-1962.
28. Bennett, M. S., H. L. Ng, A. Ali, and O. O. Yang. 2008. Cross-clade detection of HIV-1-specific cytotoxic T lymphocytes does not reflect cross-clade antiviral activity. J. Infect. Dis. 197: 390-397.
29. Mailliard, R. B., K. N. Smith, R. J. Fecek, G. Rappocciolo, E. J. Nascimento, E. T. Marques, S. C. Watkins, J. I. Mullins, and C. R. Rinaldo. 2013. Selective induction of CTL helper rather than killer activity by natural epitope variants promotes dendritic cell-mediated HIV-1 dissemination. J. Immunol. 191: 2570-2580.
30. Malhotra, U., J. Nolin, J. I. Mullins, and M. J. McElrath. 2007. Comprehensive epitope analysis of cross-clade Gag-specific T-cell responses in individuals with early HIV-1 infection in the US epidemic. Vaccine 25: 381-390.
31. Turk, G., M. M. Gherardi, N. Laufer, M. Saracco, R. Luzzi, J. H. Cox, P. Cahn, and H. Salomon. 2008. Magnitude, breadth, and functional profile of T-cell responses during human immunodeficiency virus primary infection with B and BF viral variants. J. Virol. 82: 2853-2866.
32. Doroudchi, M., O. Yegorov, T. Baumgartner, A. E. Kernaleguen, G. Breton, M. L. Ndongala, M. R. Boulassel, J. P. Routy, N. F. Bernard, R. P. Sékaly, and B. Yassine-Diab. 2012. Autologous HIV-1 clade-B Nef peptides elicit increased frequency, breadth and function of CD8+ T-cells compared to consensus peptides. PLoS One 7: e49562.
33. McMichael, A. J., P. Borrow, G. D. Tomaras, N. Goonetilleke, and B. F. Haynes. 2010. The immune response during acute HIV-1 infection: clues for vaccine development. Nat. Rev. Immunol. 10: 11-23.
34. Salazar-Gonzalez, J. F., M. G. Salazar, B. F. Keele, G. H. Learn, E. E. Giorgi, H. Li, J. M. Decker, S. Wang, J. Baalwa, M. H. Kraus, et al. 2009. Genetic identity, biological phenotype, and evolutionary pathways of transmitted/founder viruses in acute and early HIV-1 infection. J. Exp. Med. 206: 1273-1289.
35. Betts, M. R., B. Exley, D. A. Price, A. Bansal, Z. T. Camacho, V. Teaberry, S. M. West, D. R. Ambrozak, G. Tomaras, M. Roederer, et al. 2005. Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection. Proc. Natl. Acad. Sci. USA 102: 4512-4517.
36. Bansal, A., J. Carlson, J. Yan, O. T. Akinsiku, M. Schaefer, S. Sabbaj, A. Bet, D. N. Levy, S. Heath, J. Tang, et al. 2010. CD8 T cell response and evolutionary pressure to HIV-1 cryptic epitopes derived from antisense transcription. J. Exp. Med. 207: 51-59.
37. Bansal, A., L. Yue, J. Conway, K. Yusim, J. Tang, J. Kappes, R. A. Kaslow, C. M. Wilson, and P. A. Goepfert. 2007. Immunological control of chronic HIV-1 infection: HLA-mediated immune function and viral evolution in adolescents. AIDS 21: 2387-2397.
38. Almeida, J. R., D. Sauce, D. A. Price, L. Papagno, S. Y. Shin, A. Moris, M. Larsen, G. Pancino, D. C. Douek, B. Autran, et al. 2009. Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity. Blood 113: 6351-6360.
39. Akinsiku, O. T., A. Bansal, S. Sabbaj, S. L. Heath, and P. A. Goepfert. 2011. Interleukin-2 production by polyfunctional HIV-1-specific CD8 T cells is associated with enhanced viral suppression. J. Acquir. Immune Defic. Syndr. 58: 132-140.
40. Bansal, A., B. Jackson, K. West, S. Wang, S. Lu, J. S. Kennedy, and P. A. Goepfert. 2008. Multifunctional T-cell characteristics induced by a polyvalent DNA prime/protein boost human immunodeficiency virus type 1 vaccine regimen given to healthy adults are dependent on the route and dose of administration. J. Virol. 82: 6458-6469.
41. Kim, G. G., V. S. Donnenberg, A. D. Donnenberg, W. Gooding, and T. L. Whiteside. 2007. A novel multiparametric flow cytometry-based cytotoxicity assay simultaneously immunophenotypes effector cells: comparisons to a 4 h 51Cr-release assay. J. Immunol. Methods 325: 51-66.
42. Lecoeur, H., M. Février, S. Garcia, Y. Rivière, and M. L. Gougeon. 2001. A novel flow cytometric assay for quantitation and multiparametric characterization of cell-mediated cytotoxicity. J. Immunol. Methods 253: 177-187.
43. Gras, S., S. R. Burrows, L. Kjer-Nielsen, C. S. Clements, Y. C. Liu, L. C. Sullivan, M. J. Bell, A. G. Brooks, A. W. Purcell, J. McCluskey, and J. Rossjohn. 2009. The shaping of T cell receptor recognition by self-tolerance. Immunity 30: 193-203.
44. Kabsch, W. 2010. Integration, scaling, space-group assignment and post-refinement. Acta Crystallogr. D Biol. Crystallogr. 66: 133-144.
45. Evans, P. 2006. Scaling and assessment of data quality. Acta Crystallogr. D Biol. Crystallogr. 62: 72-82.
46. Price, D. A., J. M. Brenchley, L. E. Ruff, M. R. Betts, B. J. Hill, M. Roederer, R. A. Koup, S. A. Migueles, E. Gostick, L. Wooldridge, et al. 2005. Avidity for antigen shapes clonal dominance in CD8+ T cell populations specific for persistent DNA viruses. J. Exp. Med. 202: 1349-1361.
47. Price, D. A., S. M. West, M. R. Betts, L. E. Ruff, J. M. Brenchley, D. R. Ambrozak, Y. Edghill-Smith, M. J. Kuroda, D. Bogdan, K. Kunstman, et al. 2004. T cell receptor recognition motifs govern immune escape patterns in acute SIV infection. Immunity 21: 793-803.
48. Lefranc, M. P., C. Pommié, M. Ruiz, V. Giudicelli, E. Foulquier, L. Truong, V. Thouvenin-Contet, and G. Lefranc. 2003. IMGT unique numbering for immunoglobulin and T cell receptor variable domains and Ig superfamily V-like domains. Dev. Comp. Immunol. 27: 55-77.
49. Carlson, J. M., V. Y. Du, N. Pfeifer, A. Bansal, V. Y. Tan, K. Power, C. J. Brumme, A. Kreimer, C. E. DeZiel, N. Fusi, et al. Nat. Med. In press.
50. Betts, M. R., M. C. Nason, S. M. West, S. C. De Rosa, S. A. Migueles, J. Abraham, M. M. Lederman, J. M. Benito, P. A. Goepfert, M. Connors, et al. 2006. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 107: 4781-4789.
51. Riou, C., W. A. Burgers, K. Mlisana, R. A. Koup, M. Roederer, S. S. Abdool Karim, C. Williamson, and C. M. Gray. 2014. Differential impact of magnitude, polyfunctional capacity, and specificity of HIV-specific CD8+ T cell responses on HIV set point. J. Virol. 88: 1819-1824.
52. Paul, S., D. Weiskopf, M. A. Angelo, J. Sidney, B. Peters, and A. Sette. 2013. HLA class I alleles are associated with peptide-binding repertoires of different size, affinity, and immunogenicity. J. Immunol. 191: 5831-5839.
53. Sette, A., A. Vitiello, B. Reherman, P. Fowler, R. Nayersina, W. M. Kast, C. J. Melief, C. Oseroff, L. Yuan, J. Ruppert, et al. 1994. The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J. Immunol. 153: 5586-5592.
54. Foley, M. H., T. Forcier, E. McAndrew, M. Gonzalez, H. Chen, B. Juelg, B. D. Walker, and D. J. Irvine. 2014. High avidity CD8+ T cells efficiently eliminate motile HIV-infected targets and execute a locally focused program of anti-viral function. PLoS One 9: e87873.
55. Berger, C. T., N. Frahm, D. A. Price, B. Mothe, M. Ghebremichael, K. L. Hartman, L. M. Henry, J. M. Brenchley, L. E. Ruff, V. Venturi, et al. 2011. High-functionalavidity cytotoxic T lymphocyte responses to HLA-B-restricted Gag-derived epitopes associated with relative HIV control. J. Virol. 85: 9334-9345.
56. Viganò, S., D. T. Utzschneider, M. Perreau, G. Pantaleo, D. Zehn, and A. Harari. 2012. Functional avidity: a measure to predict the efficacy of effector T cells? Clin. Dev. Immunol. 2012: 153863.
57. Maile, R., C. A. Siler, S. E. Kerry, K. E. Midkiff, E. J. Collins, and J. A. Frelinger. 2005. Peripheral "CD8 tuning" dynamically modulates the size and responsiveness of an antigen-specific T cell pool in vivo. J. Immunol. 174: 619-627.
58. Iglesias, M. C., J. R. Almeida, S. Fastenackels, D. J. van Bockel, M. Hashimoto, V. Venturi, E. Gostick, A. Urrutia, L. Wooldridge, M. Clement, et al. 2011. Escape from highly effective public CD8+ T-cell clonotypes by HIV. Blood 118: 2138-2149.
59. Almeida, J. R., D. A. Price, L. Papagno, Z. A. Arkoub, D. Sauce, E. Bornstein, T. E. Asher, A. Samri, A. Schnuriger, I. Theodorou, et al. 2007. Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J. Exp. Med. 204: 2473-2485.
60. Altfeld, M., E. T. Kalife, Y. Qi, H. Streeck, M. Lichterfeld, M. N. Johnston, N. Burgett, M. E. Swartz, A. Yang, G. Alter, et al. 2006. HLA alleles associated with delayed progression to AIDS contribute strongly to the initial CD8+ T cell response against HIV-1. PLoS Med. 3: e403.
61. Goulder, P. J., C. Brander, Y. Tang, C. Tremblay, R. A. Colbert, M. M. Addo, E. S. Rosenberg, T. Nguyen, R. Allen, A. Trocha, et al. 2001. Evolution and transmission of stable CTL escape mutations in HIV infection. Nature 412: 334-338.
62. Costa, A. I., D. Koning, K. Ladell, J. E. McLaren, B. P. Grady, I. M. Schellens, P. van Ham, M. Nijhuis, J. A. Borghans, C. Keşmir, et al. 2015. Complex T-cell receptor repertoire dynamics underlie the CD8+ T-cell response to HIV-1. J. Virol. 89: 110-119.
63. Davenport, M. P., D. A. Price, and A. J. McMichael. 2007. The T cell repertoire in infection and vaccination: implications for control of persistent viruses. Curr. Opin. Immunol. 19: 294-300.
64. Kilby, J. M., H. Y. Lee, J. D. Hazelwood, A. Bansal, R. P. Bucy, M. S. Saag, G. M. Shaw, E. P. Acosta, V. A. Johnson, A. S. Perelson, and P. A. Goepfert, UAB Acute Infection, Early Disease Research Program (AIEDRP) Group. 2008. Treatment response in acute/early infection versus advanced AIDS: equivalent first and second phases of HIV RNA decline. AIDS 22: 957-962.
65. Henn, M. R., C. L. Boutwell, P. Charlebois, N. J. Lennon, K. A. Power, A. R. Macalalad, A. M. Berlin, C. M. Malboeuf, E. M. Ryan, S. Gnerre, et al. 2012. Whole genome deep sequencing of HIV-1 reveals the impact of early minor variants upon immune recognition during acute infection. PLoS Pathog. 8: e1002529.
66. Goonetilleke, N., M. K. Liu, J. F. Salazar-Gonzalez, G. Ferrari, E. Giorgi, V. V. Ganusov, B. F. Keele, G. H. Learn, E. L. Turnbull, M. G. Salazar, et al; CHAVI Clinical Core B. 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.
67. Milicic, A., D. A. Price, P. Zimbwa, B. L. Booth, H. L. Brown, P. J. Easterbrook, K. Olsen, N. Robinson, U. Gileadi, A. K. Sewell, et al. 2005. CD8+ T cell epitope-flanking mutations disrupt proteasomal processing of HIV-1 Nef. J. Immunol. 175: 4618-4626.
68. Martinez, A. N., S. Tenzer, and H. Schild. 2009. T-cell epitope processing (the epitope flanking regions matter). Methods Mol. Biol. 524: 407-415.
69. Allen, T. M., M. Altfeld, X. G. Yu, K. M. O'Sullivan, M. Lichterfeld, S. Le Gall, M. John, B. R. Mothe, P. K. Lee, E. T. Kalife, et al. 2004. Selection, transmission, and reversion of an antigen-processing cytotoxic T-lymphocyte escape mutation in human immunodeficiency virus type 1 infection. J. Virol. 78: 7069-7078.
70. Bronke, C., C. A. Almeida, E. McKinnon, S. G. Roberts, N. M. Keane, A. Chopra, J. M. Carlson, D. Heckerman, S. Mallal, and M. John. 2013. HIV escape mutations occur preferentially at HLA-binding sites of CD8 T-cell epitopes. AIDS 27: 899-905.
71. Turner, S. J., P. C. Doherty, J. McCluskey, and J. Rossjohn. 2006. Structural determinants of T-cell receptor bias in immunity. Nat. Rev. Immunol. 6: 883-894.
72. Motozono, C., J. S. Bridgeman, D. A. Price, A. K. Sewell, and T. Ueno. 2015. Clonotypically similar hybrid ab T cell receptors can exhibit markedly different surface expression, antigen specificity and cross-reactivity. Clin. Exp. Immunol. 180: 560-570.
73. Price, D. A., T. E. Asher, N. A. Wilson, M. C. Nason, J. M. Brenchley, I. S. Metzler, V. Venturi, E. Gostick, P. K. Chattopadhyay, M. Roederer, et al. 2009. Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection. J. Exp. Med. 206: 923-936.
74. Barouch, D. H., K. L. O'Brien, N. L. Simmons, S. L. King, P. Abbink, L. F. Maxfield, Y. H. Sun, A. La Porte, A. M. Riggs, D. M. Lynch, et al. 2010. Mosaic HIV-1 vaccines expand the breadth and depth of cellular immune responses in rhesus monkeys. Nat. Med. 16: 319-323.
75. Santra, S., H. X. Liao, R. Zhang, M. Muldoon, S. Watson, W. Fischer, J. Theiler, J. Szinger, H. Balachandran, A. Buzby, et al. 2010. Mosaic vaccines elicit CD8+ T lymphocyte responses that confer enhanced immune coverage of diverse HIV strains in monkeys. Nat. Med. 16: 324-328.