Polyfunctional CD8+ T-Cell Response to Autologous Peptides from Protease and Reverse Transcriptase of HIV-1 Clade B

Author(s): Liliana Acevedo-Saenz, Federico Perdomo-Celis, Carlos J. Montoya, Paula A. Velilla*.

Journal Name: Current HIV Research

Volume 17 , Issue 5 , 2019

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Abstract:

Background: The diversity of the HIV proteome influences the cellular response and development of an effective vaccine, particularly due to the generation of viral variants with mutations located within CD8+ T-cell epitopes. These mutations can affect the recognition of the epitopes, that may result in the selection of HIV variants with mutated epitopes (autologous epitopes) and different CD8+ T-cell functional profiles.

Objective: To determine the phenotype and functionality of CD8+ T-cell from HIV-infected Colombian patients in response to autologous and consensus peptides derived from HIV-1 clade B protease and reverse transcriptase (RT).

Methods: By flow cytometry, we compared the ex vivo CD8+ T-cell responses from HIV-infected patients to autologous and consensus peptides derived from HIV-1 clade B protease and RT, restricted by HLA-B*35, HLA-B*44 and HLA-B*51 alleles.

Results: Although autologous peptides restricted by HLA-B*35 and HLA-B*44 did not show any differences compared with consensus peptides, we observed the induction of a higher polyfunctional profile of CD8+ T-cells by autologous peptides restricted by HLA-B*51, particularly by the production of interferon-γ and macrophage inflammatory protein-1β. The response by different memory CD8+ T-cell populations was comparable between autologous vs. consensus peptides. In addition, the magnitude of the polyfunctional response induced by the HLA-B*51-restricted QRPLVTIRI autologous epitope correlated with low viremia.

Conclusion: Autologous peptides should be considered for the evaluation of HIV-specific CD8+ Tcell responses and to reveal some relevant epitopes that could be useful for therapeutic strategies aiming to promote polyfunctional CD8+ T-cell responses in a specific population of HIV-infected patients.

Keywords: HIV, CD8+ T-cells, protease, reverse transcriptase, HLA-B, autologous, consensus.

[1]
Kaur G, Mehra N. Genetic determinants of HIV-1 infection and progression to AIDS: susceptibility to HIV infection. Tissue Antigens 2009; 73(4): 289-301.
[http://dx.doi.org/10.1111/j.1399-0039.2009.01220.x] [PMID: 19317737]
[2]
Kaur G, Mehra N. Genetic determinants of HIV-1 infection and progression to AIDS: immune response genes. Tissue Antigens 2009; 74(5): 373-85.
[http://dx.doi.org/10.1111/j.1399-0039.2009.01337.x] [PMID: 19765261]
[3]
Goulder PJR, Watkins DI. Impact of MHC class I diversity on immune control of immunodeficiency virus replication. Nat Rev Immunol 2008; 8(8): 619-30.
[http://dx.doi.org/10.1038/nri2357] [PMID: 18617886]
[4]
Chakraborty S, Rahman T, Chakravorty R. Characterization of the Protective HIV-1 CTL Epitopes and the Corresponding HLA Class I Alleles: A Step towards Designing CTL Based HIV-1 Vaccine. Adv Virol 2014.2014321974
[http://dx.doi.org/10.1155/2014/321974] [PMID: 24744786]
[5]
Payne RP, Matthews PC, Prado JG, Goulder PJR. HLA-mediated control of HIV and HIV adaptation to HLA. Adv Parasitol 2009; 68: 1-20.
[http://dx.doi.org/10.1016/S0065-308X(08)00601-5] [PMID: 19289188]
[6]
Kaslow RA, Carrington M, Apple R, et al. Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat Med 1996; 2(4): 405-11.
[http://dx.doi.org/10.1038/nm0496-405] [PMID: 8597949]
[7]
Kiepiela P, Leslie AJ, Honeyborne I, et al. Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 2004; 432(7018): 769-75.
[http://dx.doi.org/10.1038/nature03113] [PMID: 15592417]
[8]
Walker B, McMichael A. The T-cell response to HIV. Cold Spring Harb Perspect Med 2012; 2(11): 1-19.
[http://dx.doi.org/10.1101/cshperspect.a007054] [PMID: 23002014]
[9]
Brumme ZL, John M, Carlson JM, et al. HLA-associated immune escape pathways in HIV-1 subtype B Gag, Pol and Nef proteins. PLoS One 2009; 4(8)e6687
[http://dx.doi.org/10.1371/journal.pone.0006687] [PMID: 19690614]
[10]
Jones NA, Wei X, Flower DR, et al. Determinants of human immunodeficiency virus type 1 escape from the primary CD8+ cytotoxic T lymphocyte response. J Exp Med 2004; 200(10): 1243-56.
[http://dx.doi.org/10.1084/jem.20040511] [PMID: 15545352]
[11]
Goulder PJR, Phillips RE, Colbert RA, et al. Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat Med 1997; 3(2): 212-7.
[http://dx.doi.org/10.1038/nm0297-212] [PMID: 9018241]
[12]
Arcia D, Acevedo-Sáenz L, Rugeles MT, Velilla PA. Role of CD8+ T Cells in the Selection of HIV-1 Immune Escape Mutations. Viral Immunol 2017; 30(1): 3-12.
[http://dx.doi.org/10.1089/vim.2016.0095] [PMID: 27805477]
[13]
Koga M, Kawana-Tachikawa A, Heckerman D, et al. Changes in impact of HLA class I allele expression on HIV-1 plasma virus loads at a population level over time. Microbiol Immunol 2010; 54(4): 196-205.
[http://dx.doi.org/10.1111/j.1348-0421.2010.00206.x] [PMID: 20377748]
[14]
Kawashima Y, Pfafferott K, Frater J, et al. Adaptation of HIV-1 to human leukocyte antigen class I. Nature 2009; 458(7238): 641-5.
[http://dx.doi.org/10.1038/nature07746] [PMID: 19242411]
[15]
Addo MM, Yu XG, Rathod A, et al. Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load. J Virol 2003; 77(3): 2081-92.
[http://dx.doi.org/10.1128/JVI.77.3.2081-2092.2003] [PMID: 12525643]
[16]
Kiepiela P, Ngumbela K, Thobakgale C, et al. CD8+ T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med 2007; 13(1): 46-53.
[http://dx.doi.org/10.1038/nm1520] [PMID: 17173051]
[17]
Payne RP, Kløverpris H, Sacha JB, et al. Efficacious Early Antiviral Activity of HIV Gag- and Pol-Specific HLA-B*2705-Restricted CD8+ T Cells. J Virol 2010 Oct 15;; 84(20): 10543-57.
[http://dx.doi.org/10.1128/JVI.00793-10] [PMID: 20686036]
[18]
Doroudchi M, Yegorov O, Baumgartner T, et al. Autologous HIV-1 clade-B Nef peptides elicit increased frequency, breadth and function of CD8+ T-cells compared to consensus peptides. PLoS One 2012; 7(11)e49562
[http://dx.doi.org/10.1371/journal.pone.0049562] [PMID: 23185362]
[19]
Altfeld M, Addo MM, Shankarappa R, et al. Enhanced detection of human immunodeficiency virus type 1-specific T-cell responses to highly variable regions by using peptides based on autologous virus sequences. J Virol 2003; 77(13): 7330-40.
[http://dx.doi.org/10.1128/JVI.77.13.7330-7340.2003] [PMID: 12805431]
[20]
Rojas W, Parra MV, Campo O, et al. Genetic make up and structure of Colombian populations by means of uniparental and biparental DNA markers. Am J Phys Anthropol 2010; 143(1): 13-20.
[http://dx.doi.org/10.1002/ajpa.21270] [PMID: 20734436]
[21]
Acevedo-Sáenz L, Ochoa R, Rugeles MT, Olaya-García P, Velilla-Hernández PA, Diaz FJ. Selection pressure in CD8+ T-cell epitopes in the pol gene of HIV-1 infected individuals in Colombia. A bioinformatic approach. Viruses 2015; 7(3): 1313-31.
[http://dx.doi.org/10.3390/v7031313] [PMID: 25803098]
[22]
Perdomo-Celis F, Velilla PA, Taborda NA, Rugeles MT. An altered cytotoxic program of CD8+ T-cells in HIV-infected patients despite HAART-induced viral suppression. PLoS One 2019; 14(1)e0210540
[http://dx.doi.org/10.1371/journal.pone.0210540] [PMID: 30625227]
[23]
Roederer M, Nozzi JL, Nason MC. SPICE: exploration and analysis of post-cytometric complex multivariate datasets. Cytometry A 2011; 79(2): 167-74.
[http://dx.doi.org/10.1002/cyto.a.21015] [PMID: 21265010]
[24]
Arcia D, Ochoa R, Hernández JC, et al. Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia. Infect Genet Evol 2019; 69: 267-78.
[http://dx.doi.org/10.1016/j.meegid.2018.07.001] [PMID: 30808498]
[25]
Sallusto F, Lenig D, Förster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions. Nature 1999; 401(6754): 708-12.
[http://dx.doi.org/10.1038/44385] [PMID: 10537110]
[26]
Chen G, Shankar P, Lange C, et al. CD8 T cells specific for human immunodeficiency virus, Epstein-Barr virus, and cytomegalovirus lack molecules for homing to lymphoid sites of infection. Blood 2001; 98(1): 156-64.
[http://dx.doi.org/10.1182/blood.V98.1.156] [PMID: 11418475]
[27]
Kersh EN, Fitzpatrick DR, Murali-Krishna K, et al. Rapid demethylation of the IFN-gamma gene occurs in memory but not naive CD8 T cells. J Immunol 2006; 176(7): 4083-93.
[http://dx.doi.org/10.4049/jimmunol.176.7.4083] [PMID: 16547244]
[28]
Kaech SM, Hemby S, Kersh E, Ahmed R. Molecular and functional profiling of memory CD8 T cell differentiation. Cell 2002; 111(6): 837-51.
[http://dx.doi.org/10.1016/S0092-8674(02)01139-X] [PMID: 12526810]
[29]
Akondy RS, Fitch M, Edupuganti S, et al. Origin and differentiation of human memory CD8 T cells after vaccination. Nature 2017; 552(7685): 362-7.
[http://dx.doi.org/10.1038/nature24633] [PMID: 29236685]
[30]
Borrow P, Lewicki H, Wei X, et al. Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat Med 1997; 3(2): 205-11.
[http://dx.doi.org/10.1038/nm0297-205] [PMID: 9018240]
[31]
Corse E, Gottschalk RA, Allison JP. Strength of TCR-peptide/MHC interactions and in vivo T cell responses. J Immunol 2011; 186(9): 5039-45.
[http://dx.doi.org/10.4049/jimmunol.1003650] [PMID: 21505216]
[32]
Rolland M, Frahm N, Nickle DC, et al. Increased breadth and depth of cytotoxic T lymphocytes responses against HIV-1-B Nef by inclusion of epitope variant sequences. PLoS One 2011; 6(3)e17969
[http://dx.doi.org/10.1371/journal.pone.0017969] [PMID: 21464919]
[33]
Turk G, Gherardi MM, Laufer N, et al. Magnitude, breadth, and functional profile of T-cell responses during human immunodeficiency virus primary infection with B and BF viral variants. J Virol 2008; 82(6): 2853-66.
[http://dx.doi.org/10.1128/JVI.02260-07] [PMID: 2258999]
[34]
Lee SK, Xu Z, Lieberman J, Shankar P. The functional CD8 T cell response to HIV becomes type-specific in progressive disease. J Clin Invest 2002; 110(9): 1339-47.
[http://dx.doi.org/10.1172/JCI0216028] [PMID: 12417573]
[35]
Karlsson I, Kløverpris H, Jensen KJ, et al. Identification of conserved subdominant HIV type 1 CD8(+) T cell epitopes restricted within common HLA supertypes for therapeutic HIV type 1 vaccines. AIDS Res Hum Retroviruses 2012; 28(11): 1434-43.
[http://dx.doi.org/10.1089/aid.2012.0081] [PMID: 22747336]
[36]
Borthwick N, Ahmed T, Ondondo B, et al. Vaccine-elicited human T cells recognizing conserved protein regions inhibit HIV-1. Mol Ther 2014; 22(2): 464-75.
[http://dx.doi.org/10.1038/mt.2013.248] [PMID: 24166483]
[37]
Papagno L, Spina CA, Marchant A, et al. Immune activation and CD8+ T-cell differentiation towards senescence in HIV-1 infection. PLoS Biol 2004; 2(2)E20
[http://dx.doi.org/10.1371/journal.pbio.0020020] [PMID: 14966528]
[38]
Sette A, Vitiello A, Reherman B, et al. The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J Immunol 1994; 153(12): 5586-92.
[PMID: 7527444]
[39]
Wang S, Li J, Chen X, Wang L, Liu W, Wu Y. Analyzing the effect of peptide-HLA-binding ability on the immunogenicity of potential CD8+ and CD4+ T cell epitopes in a large dataset. Immunol Res 2016; 64(4): 908-18.
[http://dx.doi.org/10.1007/s12026-016-8795-9] [PMID: 27094547]
[40]
Almeida JR, Sauce D, Price DA, et al. Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity. Blood 2009; 113(25): 6351-60.
[http://dx.doi.org/10.1182/blood-2009-02-206557] [PMID: 19389882]
[41]
Betts MR, Nason MC, West SM, et al. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 2006; 107(12): 4781-9.
[http://dx.doi.org/10.1182/blood-2005-12-4818] [PMID: 16467198]
[42]
Almeida JR, Price DA, Papagno L, et al. Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J Exp Med 2007; 204(10): 2473-85.
[http://dx.doi.org/10.1084/jem.20070784] [PMID: 17893201]


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VOLUME: 17
ISSUE: 5
Year: 2019
Page: [350 - 359]
Pages: 10
DOI: 10.2174/1570162X17666191017105910
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