Selection of an HLA-C*03:04-Restricted HIV-1 p24 Gag Sequence Variant Is Associated with Viral Escape from KIR2DL3+ Natural Killer Cells: Data from an Observational Cohort in South Africa

1. Cooper MA, Fehniger TA, Caligiuri MA (2001) The biology of human natural killer-cell subsets. Trends Immunol 22: 633–640. 11698225

2. Long EO, Kim HS, Liu D, Peterson ME, Rajagopalan S (2013) Controlling natural killer cell responses: integration of signals for activation and inhibition. Annu Rev Immunol 31: 227–258. doi: 10.1146/annurev-immunol-020711-075005 23516982

3. Van Teijlingen NH, Hölzemer A, Körner C, García-Beltrán WF, Schafer JL, Fadda L, et al. (2014) Sequence variations in HIV-1 p24 Gag-derived epitopes can alter binding of KIR2DL2 to HLA-C*03: 04 and modulate primary natural killer cell function. AIDS 28: 1399–1408. doi: 10.1097/QAD.0000000000000284 24785948

4. Fadda L, Borhis G, Ahmed P, Cheent K, Pageon SV, et al. (2010) Peptide antagonism as a mechanism for NK cell activation. Proc Natl Acad Sci U S A 107: 10160–10165. doi: 10.1073/pnas.0913745107 20439706

5. Fadda L, Körner C, Kumar S, van Teijlingen NH, Piechocka-Trocha A, et al. (2012) HLA-Cw*0102-restricted HIV-1 p24 epitope variants can modulate the binding of the inhibitory KIR2DL2 receptor and primary NK cell function. PLoS Pathog 8: e1002805. doi: 10.1371/journal.ppat.1002805 22807681

6. Peruzzi M, Parker KC, Long E, Mahati MS (1996) Peptide sequence requirements for the recognition of HLA-B*2705 by specific natural killer cells. J Immunol 157: 3350–3356. 8871631

7. Rajagopalan S, Long EO (1997) The direct binding of a p58 killer cell inhibitory receptor to human histocompatibility leukocyte antigen (HLA)-Cw4 exhibits peptide selectivity. J Exp Med 185: 1523–1528. 9126935

8. Stewart-Jones GBE, di Gleria K, Kollnberger S, McMichael AJ, Jones EY, et al. (2005) Crystal structures and KIR3DL1 recognition of three immunodominant viral peptides complexed to HLA-B*2705. Eur J Immunol 35: 341–351. 15657948

9. Boyington JC, Motyka SA, Schuck P, Brooks AG, Sun PD (2000) Crystal structure of an NK cell immunoglobulin-like receptor in complex with its class I MHC ligand. Nature 405: 537–543. 10850706

10. Vivian JP, Duncan RC, Berry R, O’Connor GM, Reid HH, et al. (2011) Killer cell immunoglobulin-like receptor 3DL1-mediated recognition of human leukocyte antigen B. Nature 479: 401–405. doi: 10.1038/nature10517 22020283

11. Bashirova AA, Thomas R, Carrington M (2011) HLA/KIR restraint of HIV: surviving the fittest. Annu Rev Immunol 29: 295–317. doi: 10.1146/annurev-immunol-031210-101332 21219175

12. Martin MP, Gao X, Lee J-H, Nelson GW, Detels R, et al. (2002) Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nat Genet 31: 429–434. 12134147

13. Martin MP, Qi Y, Gao X, Yamada E, Martin JN, et al. (2007) Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1. Nat Genet 39: 733–740. 17496894

14. Jennes W, Verheyden S, Mertens JW, Camara M, Seydi M, et al. (2013) Inhibitory KIR/HLA incompatibility between sexual partners confers protection against HIV-1 transmission. Blood 121: 1157–1164. doi: 10.1182/blood-2012-09-455352 23243280

15. Apps R, Qi Y, Carlson JM, Chen H, Gao X, et al. (2013) Influence of HLA-C expression level on HIV control. Science 340: 87–91. doi: 10.1126/science.1232685 23559252

16. Long BR, Ndhlovu LC, Oksenberg JR, Lanier LL, Hecht FM, et al. (2008) Conferral of enhanced natural killer cell function by KIR3DS1 in early human immunodeficiency virus type 1 infection. J Virol 82: 4785–4792. doi: 10.1128/JVI.02449-07 18305035

17. Alter G, Martin MP, Teigen N, Carr WH, Suscovich TJ, et al. (2007) Differential natural killer cell-mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes. J Exp Med 204: 3027–3036. 18025129

18. Song R, Lisovsky I, Lebouché B, Routy J-P, Bruneau J, et al. (2014) HIV protective KIR3DL1/S1-HLA-B genotypes influence NK cell-mediated inhibition of HIV replication in autologous CD4 targets. PLoS Pathog 10: e1003867. doi: 10.1371/journal.ppat.1003867 24453969

19. Colantonio AD, Bimber BN, Neidermyer WJ, Reeves RK, Alter G, et al. (2011) KIR polymorphisms modulate peptide-dependent binding to an MHC class I ligand with a Bw6 motif. PLoS Pathog 7: e1001316. doi: 10.1371/journal.ppat.1001316 21423672

20. Knapp S, Warshow U, Hegazy D, Brackenbury L, Guha IN, et al. (2010) Consistent beneficial effects of killer cell immunoglobulin-like receptor 2DL3 and group 1 human leukocyte antigen-C following exposure to hepatitis C virus. Hepatology 51: 1168–1175. doi: 10.1002/hep.23477 20077564

21. Alter G, Altfeld M (2009) NK cells in HIV-1 infection: evidence for their role in the control of HIV-1 infection. J Intern Med 265: 29–42. doi: 10.1111/j.1365-2796.2008.02045.x 19093958

22. Kamya P, Boulet S, Tsoukas CM, Routy J-P, Thomas R, et al. (2011) Receptor-ligand requirements for increased NK cell polyfunctional potential in slow progressors infected with HIV-1 coexpressing KIR3DL1*h/*y and HLA-B*57. J Virol 85: 5949–5960. doi: 10.1128/JVI.02652-10 21471235

23. Barbour JD, Sriram U, Caillier SJ, Levy JA, Hecht FM, et al. (2007) Synergy or independence? Deciphering the interaction of HLA class I and NK cell KIR alleles in early HIV-1 disease progression. PLoS Pathog 3: e43. 17447840

24. Parsons MS, Wren L, Isitman G, Navis M, Stratov I, et al. (2012) HIV infection abrogates the functional advantage of natural killer cells educated through KIR3DL1/HLA-Bw4 interactions to mediate anti-HIV antibody-dependent cellular cytotoxicity. J Virol 86: 4488–4495. doi: 10.1128/JVI.06112-11 22345455

25. Goulder PJR, Watkins DI (2008) Impact of MHC class I diversity on immune control of immunodeficiency virus replication. Nat Rev Immunol 8: 619–630. doi: 10.1038/nri2357 18617886

26. Prince JL, Claiborne DT, Carlson JM, Schaefer M, Yu T, et al. (2012) Role of transmitted Gag CTL polymorphisms in defining replicative capacity and early HIV-1 pathogenesis. PLoS Pathog 8: e1003041. doi: 10.1371/journal.ppat.1003041 23209412

27. Goepfert P, Lumm W, Farmer P, Matthews P, Prendergast A, et al. (2008) Transmission of HIV-1 Gag immune escape mutations is associated with reduced viral load in linked recipients. J Exp Med 205: 1009–1017. doi: 10.1084/jem.20072457 18426987

28. Alter G, Heckerman D, Schneidewind A, Fadda L, Kadie CM, et al. (2011) HIV-1 adaptation to NK-cell-mediated immune pressure. Nature 476: 96–100. doi: 10.1038/nature10237 21814282

29. Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, et al. (2004) Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 432: 769–775. 15592417

30. Wright JK, Brumme ZL, Carlson JM, Heckerman D, Kadie CM, et al. (2010) Gag-protease-mediated replication capacity in HIV-1 subtype C chronic infection: associations with HLA type and clinical parameters. J Virol 84: 10820–10831. doi: 10.1128/JVI.01084-10 20702636

31. Carlson JM, Brumme ZL, Rousseau CM, Brumme CJ, Matthews P, et al. (2008) Phylogenetic dependency networks: inferring patterns of CTL escape and codon covariation in HIV-1 Gag. PLoS Comput Biol 4: e1000225. doi: 10.1371/journal.pcbi.1000225 19023406

32. Carlson JM, Brumme CJ, Martin E, Listgarten J, Brockman M, et al. (2012) Correlates of protective cellular immunity revealed by analysis of population-level immune escape pathways in HIV-1. J Virol 86: 13202–13216. doi: 10.1128/JVI.01998-12 23055555

33. Storey JD, Tibshirani R. Statistical significance for genomewide studies. Proc Natl Acad Sci 2003 U S A 100: 9440–9445. 12883005

34. Storey JD, Taylor JE, Siegmund D (2004) Strong control, conservative point estimation and simultaneous conservative consistency of false discovery rates: a unified approach. J R Stat Soc Ser B Stat Methodol 66: 187–205.

35. Thielens A, Vivier E, Romagné F (2012) NK cell MHC class I specific receptors (KIR): from biology to clinical intervention. Curr Opin Immunol 24: 239–245. 22264929

36. Gatfield J, Lammert E, Nickolaus P, Münz C, Rothenfusser S, et al. (1998) Cell lines transfected with the TAP inhibitor ICP47 allow testing peptide binding to a variety of HLA class I molecules. Int Immunol 10: 1665–1672. 9846695

37. Oosten LEM, Koppers-Lalic D, Blokland E, Mulder A, Ressing ME, et al. (2007) TAP-inhibiting proteins US6, ICP47 and UL49.5 differentially affect minor and major histocompatibility antigen-specific recognition by cytotoxic T lymphocytes. Int Immunol 19: 1115–1122. 17855435

38. Alter G, Malenfant JM, Altfeld M (2004) CD107a as a functional marker for the identification of natural killer cell activity. J Immunol Methods 294: 15–22. 15604012

39. Frazier WR, Steiner N, Hou L, Dakshanamurthy S, Hurley CK (2013) Allelic variation in KIR2DL3 generates a KIR2DL2-like receptor with increased binding to its HLA-C ligand. J Immunol 190: 6198–6208. doi: 10.4049/jimmunol.1300464 23686481

40. Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, et al. (2007) CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med 13: 46–53. 17173051

41. Fernandez CS, Stratov I, De Rose R, Walsh K, Dale CJ, et al. (2005) Rapid viral escape at an immunodominant simian-human immunodeficiency virus cytotoxic T-lymphocyte epitope exacts a dramatic fitness cost J Virol 79: 5721–5731. 15827187

42. Pala P, Serwanga J, Watera C, Ritchie AJ, Moodie Z, et al. (2013) Quantitative and qualitative differences in the T cell response to HIV in uninfected Ugandans exposed or unexposed to HIV-infected partners. J Virol 87: 9053–9063. doi: 10.1128/JVI.00721-13 23760253

43. McMichael AJ (2007) Triple bypass: complicated paths to HIV escape. J Exp Med 204: 2785–2788. 18025124

44. Goulder PJ, Brander C, Tang Y, Tremblay C, Colbert RA, et al. (2001) Evolution and transmission of stable CTL escape mutations in HIV infection. Nature 412: 334–338. 11460164

45. Goulder PJR, 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. Nat Med 3: 212–217. 9018241

46. Friedrich TC, Dodds EJ, Yant LJ, Vojnov L, Rudersdorf R, et al. (2004) Reversion of CTL escape-variant immunodeficiency viruses in vivo. Nat Med 10: 275–281. 14966520

47. Honeyborne I, Codoñer FM, Leslie A, Tudor-Williams G, Luzzi G, et al. (2010) HLA-Cw*03-restricted CD8+ T-cell responses targeting the HIV-1 gag major homology region drive virus immune escape and fitness constraints compensated for by intracodon variation. J Virol 84: 11279–11288. doi: 10.1128/JVI.01144-10 20739527

48. Currier JR, Visawapoka U, Tovanabutra S, Mason CJ, Birx DL, et al. (2006) CTL epitope distribution patterns in the Gag and Nef proteins of HIV-1 from subtype A infected subjects in Kenya: use of multiple peptide sets increases the detectable breadth of the CTL response. BMC Immunol 7: 8. 16620386

49. Hoof I, Peters B, Sidney J, Pedersen LE, Sette A, et al. (2009) NetMHCpan, a method for MHC class I binding prediction beyond humans. Immunogenetics 61: 1–13. doi: 10.1007/s00251-008-0341-z 19002680

50. Verweij MC, Ressing ME, Knetsch W, Quinten E, Halenius A, et al. (2011) Inhibition of mouse TAP by immune evasion molecules encoded by non-murine herpesviruses. Mol Immunol 48: 835–845. doi: 10.1016/j.molimm.2010.12.008 21292324

51. Cohen GB, Gandhi RT, Davis DM, Mandelboim O, Chen BK, et al. (1999) The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-infected cells from NK cells. Immunity 10: 661–671. 10403641

52. Tenzer S, Crawford H, Pymm P, Gifford R, Sreenu VB, et al. (2014) HIV-1 adaptation to antigen processing results in population-level immune evasion and affects subtype diversification. Cell Rep 7: 448–463. doi: 10.1016/j.celrep.2014.03.031 24726370

53. Nakowitsch S, Quendler H, Fekete H, Kunert R, Katinger H, et al. (2005) HIV-1 mutants escaping neutralization by the in vitro experiments versus clinical studies. AIDS 19: 1957–1966.

54. Kuroishi A, Bozek K, Shioda T, Nakayama EE (2010) A single amino acid substitution of the human immunodeficiency virus type 1 capsid protein affects viral sensitivity to TRIM5 alpha. Retrovirology 7: 58. doi: 10.1186/1742-4690-7-58 20609213

55. Carrington M, Alter G (2012) Innate immune control of HIV. Cold Spring Harb Perspect Med 2: a007070. doi: 10.1101/cshperspect.a007070 22762020

56. Kulkarni S, Martin MP, Carrington M (2008) The yin and yang of HLA and KIR in human disease. Semin Immunol 20: 343–352. doi: 10.1016/j.smim.2008.06.003 18635379

57. Thananchai H, Makadzange T, Maenaka K, Kuroki K, Peng Y, et al. (2009) Reciprocal recognition of an HLA-Cw4-restricted HIV-1 gp120 epitope by CD8+ T cells and NK cells. AIDS 23: 189–193. doi: 10.1097/QAD.0b013e32831fb55a 19098488

58. Allen TM, Altfeld M, Yu XG, Kristin M, Sullivan O, 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. 15194783

59. Han C, Kawana-Tachikawa A, Shimizu A, Zhu D, Nakamura H, et al. (2014) Switching and emergence of CTL epitopes in HIV-1 infection. Retrovirology 11:38. doi: 10.1186/1742-4690-11-38 24886641

60. Pacheco Y, Allavena C, Guilloux Y, Mueller-Schmucker SM, Hueckelhoven AG, et al. (2011) The immune response to the RT181-189 epitope in HIV-1-infected patients is associated with viral sequence polymorphism flanking the epitope. J Clin Immunol 31: 681–689. doi: 10.1007/s10875-011-9520-z 21491096

61. Kanaseki T, Lind KC, Escobar H, Nagarajan N, Reyes-Vargas E, et al. (2013) ERAAP and tapasin independently edit the amino and carboxyl termini of MHC class I peptides. J Immunol 191: 1547–1555. doi: 10.4049/jimmunol.1301043 23863903

62. Boresch S, Karplus M (1995) The meaning of component analysis: decomposition of the free energy in terms of specific interactions. J Mol Biol 254: 801–807. 7500351

63. Brady GP, Sharp KA (1995) Decomposition of interaction free energies in proteins and other complex systems. J Mol Biol 254: 77–85. 7473761

64. Bren M, Florián J, Mavri J, Bren U (2007) Do all pieces make a whole? Thiele cumulants and the free energy decomposition. Theor Chem Acc 117: 535–540.

65. Xia Z, Chen H, Kang S, Huynh T, Fang JW, et al. (2014) The complex and specific pMHC interactions with diverse HIV-1 TCR clonotypes reveal a structural basis for alterations in CTL function. Sci Rep 4: 4087. doi: 10.1038/srep04087 24522437

66. Benson DM, Hofmeister CC, Padmanabhan S, Suvannasankha A, Jagannath S, et al. (2012) A phase 1 trial of the anti-KIR antibody IPH2101 in patients with relapsed/refractory multiple myeloma. Blood 120: 4324–4333. doi: 10.1182/blood-2012-06-438028 23033266

67. Kohrt HE, Thielens A, Marabelle A, Sagiv-Barfi I, Sola C, et al. (2014) Anti-KIR antibody enhancement of anti-lymphoma activity of natural killer cells as monotherapy and in combination with anti-CD20 antibodies. Blood 123: 678–686. doi: 10.1182/blood-2013-08-519199 24326534

68. Vey N, Bourhis J, Boissel N, Bordessoule D, Prebet T, et al. (2012) A phase 1 trial of the anti-inhibitory KIR mAb IPH2101 for AML in complete remission. Blood 120: 4317–4323. doi: 10.1182/blood-2012-06-437558 23002117