A Quantitative Analysis of Complexity of Human Pathogen-Specific CD4 T Cell Responses in Healthy M. tuberculosis Infected South Africans

PLoS Pathogens

Volumn 12, Issue 7, 2016, Pages

  Lindestam Arlehamn, Cecilia S ^a   McKinney, Denise M ^a   Carpenter, Chelsea ^a   Paul, Sinu ^a   Rozot, Virginie ^b   Makgotlho, Edward ^b   Gregg, Yolande ^b   van Rooyen, Michele ^b   Ernst, Joel D ^c   Hatherill, Mark ^b   Hanekom, Willem A ^b   Peters, Bjoern ^a   Scriba, Thomas J ^b   Sette, Alessandro ^a  

^a LA JOLLA INSTITUTE FOR ALLERGY AND IMMUNOLOGY   (United States)

^b UNIVERSITY OF CAPE TOWN   (South Africa)

^c NEW YORK UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BCG VACCINE; EPITOPE; GAMMA INTERFERON; HLA ANTIGEN CLASS 2; INTERLEUKIN 10; INTERLEUKIN 17; INTERLEUKIN 5; BACTERIAL ANTIGEN; HLA ANTIGEN; MYCOBACTERIUM TUBERCULOSIS ANTIGENS;

ADULT; AGED; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL VIABILITY; CONTROLLED STUDY; ENZYME LINKED IMMUNOSPOT ASSAY; FEMALE; FLOW CYTOMETRY; HLA TYPING; HUMAN; HUMAN CELL; IMMUNE RESPONSE; IMMUNOGENICITY; IMMUNOREACTIVITY; INTERFERON GAMMA RELEASE ASSAY; MALE; MYCOBACTERIUM TUBERCULOSIS; NORMAL HUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PROTEIN EXPRESSION; QUANTITATIVE ANALYSIS; TUBERCULOSIS; YOUNG ADULT; FLUORESCENT ANTIBODY TECHNIQUE; IMMUNOLOGY; SOUTH AFRICA;

ADULT; ANTIGENS, BACTERIAL; CD4-POSITIVE T-LYMPHOCYTES; ENZYME-LINKED IMMUNOSPOT ASSAY; EPITOPES, T-LYMPHOCYTE; FEMALE; FLUORESCENT ANTIBODY TECHNIQUE; HLA ANTIGENS; HUMANS; MALE; MYCOBACTERIUM TUBERCULOSIS; SOUTH AFRICA; TUBERCULOSIS;

EID: 84982943706     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1005760     Document Type: Article

References (73)

1. Sallusto F, Geginat J, Lanzavecchia A, (2004) Central Memory and Effector Memory T Cell Subsets: Function, Generation, and Maintenance. Annual Review of Immunology22: 745–763. 15032595
2. Zhu J, Yamane H, Paul WE, (2010) Differentiation of effector CD4 T cell populations (*). Annu Rev Immunol28: 445–489. doi: 10.1146/annurev-immunol-030409-10121220192806
3. Bendall SC, Simonds EF, Qiu P, Amir el AD, Krutzik PO, et al. (2011) Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum. Science332: 687–696. doi: 10.1126/science.119870421551058
4. Newell Evan W, Sigal N, Bendall Sean C, Nolan Garry P, Davis Mark M, (2012) Cytometry by Time-of-Flight Shows Combinatorial Cytokine Expression and Virus-Specific Cell Niches within a Continuum of CD8+ T Cell Phenotypes. Immunity36: 142–152. doi: 10.1016/j.immuni.2012.01.00222265676
5. Yao Y, Liu R, Shin MS, Trentalange M, Allore H, et al. (2014) CyTOF supports efficient detection of immune cell subsets from small samples. J Immunol Methods415: 1–5. doi: 10.1016/j.jim.2014.10.01025450003
6. Saliba AE, Westermann AJ, Gorski SA, Vogel J, (2014) Single-cell RNA-seq: advances and future challenges. Nucleic Acids Res42: 8845–8860. doi: 10.1093/nar/gku55525053837
7. Buettner F, Natarajan KN, Casale FP, Proserpio V, Scialdone A, et al. (2015) Computational analysis of cell-to-cell heterogeneity in single-cell RNA-sequencing data reveals hidden subpopulations of cells. Nat Biotechnol33: 155–160. doi: 10.1038/nbt.310225599176
8. Arlehamn CL, Seumois G, Gerasimova A, Huang C, Fu Z, et al. (2014) Transcriptional Profile of Tuberculosis Antigen-Specific T Cells Reveals Novel Multifunctional Features. J Immunol.
9. Dillon MB, Schulten V, Oseroff C, Paul S, Dullanty LM, et al. (2015) Different Bla-g T cell antigens dominate responses in asthma versus rhinitis subjects. Clin Exp Allergy.
10. Lindestam Arlehamn CS, Gerasimova A, Mele F, Henderson R, Swann J, et al. (2013) Memory T Cells in Latent Mycobacterium tuberculosis Infection Are Directed against Three Antigenic Islands and Largely Contained in a CXCR3+CCR6+ Th1 Subset. PLoS Pathog9: e1003130. doi: 10.1371/journal.ppat.100313023358848
11. Weiskopf D, Angelo MA, de Azeredo EL, Sidney J, Greenbaum JA, et al. (2013) Comprehensive analysis of dengue virus-specific responses supports an HLA-linked protective role for CD8+ T cells. Proceedings of the National Academy of Sciences of the United States of America110: E2046–2053. doi: 10.1073/pnas.130522711023580623
12. Schulten V, Greenbaum JA, Hauser M, McKinney DM, Sidney J, et al. (2013) Previously undescribed grass pollen antigens are the major inducers of T helper 2 cytokine-producing T cells in allergic individuals. Proc Natl Acad Sci U S A110: 3459–3464. doi: 10.1073/pnas.130051211023401558
13. Marsh SG, Parham P., Barber L.D, . (2000) The HLA FactsBook. London: Academic Press.
14. Robinson J, Mistry K, McWilliam H, Lopez R, Parham P, et al. (2011) The IMGT/HLA database. Nucleic Acids Res39: D1171–1176. doi: 10.1093/nar/gkq99821071412
15. Hinz D, Oseroff C, Pham J, Sidney J, Peters B, et al. (2015) Definition of a pool of epitopes that recapitulates the T cell reactivity against major house dust mite allergens. Clin Exp Allergy45: 1601–1612. doi: 10.1111/cea.1250725652035
16. Oseroff C, Sidney J, Tripple V, Grey H, Wood R, et al. (2012) Analysis of T cell responses to the major allergens from German cockroach: epitope specificity and relationship to IgE production. Journal of immunology189: 679–688.
17. Moutaftsi M, Bui H-H, Peters B, Sidney J, Salek-Ardakani S, et al. (2007) Vaccinia Virus-Specific CD4+ T Cell Responses Target a Set of Antigens Largely Distinct from Those Targeted by CD8+ T Cell Responses. The Journal of Immunology178: 6814–6820. 17513729
18. Kotturi MF, Scott I, Wolfe T, Peters B, Sidney J, et al. (2008) Naive precursor frequencies and MHC binding rather than the degree of epitope diversity shape CD8+ T cell immunodominance. J Immunol181: 2124–2133. 18641351
19. Yewdell JW, (2006) Confronting complexity: real-world immunodominance in antiviral CD8+ T cell responses. Immunity25: 533–543. 17046682
20. Assarsson E, Sidney J, Oseroff C, Pasquetto V, Bui H-H, et al. (2007) A Quantitative Analysis of the Variables Affecting the Repertoire of T Cell Specificities Recognized after Vaccinia Virus Infection. J Immunol178: 7890–7901. 17548627
21. WHO (2015) Global Tuberculosis Report 2015.
22. Andrews JR, Morrow C, Walensky RP, Wood R, (2014) Integrating social contact and environmental data in evaluating tuberculosis transmission in a South African township. J Infect Dis210: 597–603. doi: 10.1093/infdis/jiu13824610874
23. Ottenhoff TH, Verreck FA, Hoeve MA, van de Vosse E, (2005) Control of human host immunity to mycobacteria. Tuberculosis (Edinb)85: 53–64.
24. Casanova JL, Holland SM, Notarangelo LD, (2012) Inborn errors of human JAKs and STATs. Immunity36: 515–528. doi: 10.1016/j.immuni.2012.03.01622520845
25. Newport MJ, Huxley CM, Huston S, Hawrylowicz CM, Oostra BA, et al. (1996) A Mutation in the Interferon-γ –Receptor Gene and Susceptibility to Mycobacterial Infection. N Engl J Med335: 1941–1949. 8960473
26. Okada S, Markle JG, Deenick EK, Mele F, Averbuch D, et al. (2015) IMMUNODEFICIENCIES. Impairment of immunity to Candida and Mycobacterium in humans with bi-allelic RORC mutations. Science349: 606–613. doi: 10.1126/science.aaa428226160376
27. van Crevel R, Karyadi E, Preyers F, Leenders M, Kullberg BJ, et al. (2000) Increased Production of Interleukin 4 by CD4+ and CD8+ T Cells from Patients with Tuberculosis Is Related to the Presence of Pulmonary Cavities. The Journal of Infectious Diseases181: 1194–1197. 10720554
28. Ordway DJ, Costa L, Martins M, Silveira H, Amaral L, et al. (2004) Increased Interleukin‚Äê4 Production by CD8 and Œ≥Œ¥ T Cells in Health‚ÄêCare Workers Is Associated with the Subsequent Development of Active Tuberculosis. The Journal of Infectious Diseases190: 756–766. 15272404
29. Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, et al. (2007) Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol8: 639–646. 17486092
30. Basile JI, Geffner LJ, Romero MM, Balboa L, Sabio YGC, et al. (2011) Outbreaks of mycobacterium tuberculosis MDR strains induce high IL-17 T-cell response in patients with MDR tuberculosis that is closely associated with high antigen load. The Journal of infectious diseases204: 1054–1064. doi: 10.1093/infdis/jir46021881121
31. Jurado JO, Pasquinelli V, Alvarez IB, Peña D, Rovetta AI, et al. (2012) IL-17 and IFN-γ expression in lymphocytes from patients with active tuberculosis correlates with the severity of the disease. Journal of Leukocyte Biology.
32. Scriba TJ, Kalsdorf B, Abrahams D-A, Isaacs F, Hofmeister J, et al. (2008) Distinct, Specific IL-17- and IL-22-Producing CD4+ T Cell Subsets Contribute to the Human Anti-Mycobacterial Immune Response. J Immunol180: 1962–1970. 18209095
33. Redford PS, Murray PJ, O'Garra A, (2011) The role of IL-10 in immune regulation during M. tuberculosis infection. Mucosal immunology4: 261–270. doi: 10.1038/mi.2011.721451501
34. Verbon A, Juffermans N, Van Deventer SJ, Speelman P, Van Deutekom H, et al. (1999) Serum concentrations of cytokines in patients with active tuberculosis (TB) and after treatment. Clinical and experimental immunology115: 110–113. 9933428
35. Lindestam Arlehamn CS, Sidney J, Henderson R, Greenbaum JA, James EA, et al. (2012) Dissecting Mechanisms of Immunodominance to the Common Tuberculosis Antigens ESAT-6, CFP10, Rv2031c (hspX), Rv2654c (TB7.7), and Rv1038c (EsxJ). The Journal of Immunology188: 5020–5031. doi: 10.4049/jimmunol.110355622504645
36. Lew JM, Kapopoulou A, Jones LM, Cole ST, (2011) TubercuList– 10 years after. Tuberculosis91: 1–7. doi: 10.1016/j.tube.2010.09.00820980199
37. Bitter W, Houben ENG, Bottai D, Brodin P, Brown EJ, et al. (2009) Systematic Genetic Nomenclature for Type VII Secretion Systems. PLoS Pathog5: e1000507. doi: 10.1371/journal.ppat.100050719876390
38. Lalvani A, Nagvenkar P, Udwadia Z, Pathan AA, Wilkinson KA, et al. (2001) Enumeration of T Cells Specific for RD1-Encoded Antigens Suggests a High Prevalence of Latent Mycobacterium tuberculosis Infection in Healthy Urban Indians. J Infect Dis183: 469–477. 11133379
39. Mustafa AS, (2009) Th1 cell reactivity and HLA-DR binding prediction for promiscuous recognition of MPT63 (Rv1926c), a major secreted protein of Mycobacterium tuberculosis. Scand J Immunol69: 213–222. doi: 10.1111/j.1365-3083.2008.02221.x19281533
40. Mustafa AS, Al-Attiyah Ra, Hanif SNM, Shaban FA, (2008) Efficient Testing of Large Pools of Mycobacterium tuberculosis RD1 Peptides and Identification of Major Antigens and Immunodominant Peptides Recognized by Human Th1 Cells. Clin Vaccine Immunol15: 916–924. doi: 10.1128/CVI.00056-0818400977
41. Cuccu B, Freer G, Genovesi A, Garzelli C, Rindi L, (2011) Identification of a human immunodominant T-cell epitope of mycobacterium tuberculosis antigen PPE44. BMC Microbiol11: 167. doi: 10.1186/1471-2180-11-16721787411
42. Oseroff C, Sidney J, Kotturi MF, Kolla R, Alam R, et al. (2010) Molecular determinants of T cell epitope recognition to the common Timothy grass allergen. J Immunol185: 943–955. doi: 10.4049/jimmunol.100040520554959
43. Behr M, Wilson M, Gill W, Salamon H, Schoolnik G, et al. (1999) Comparative genomics of BCG vaccines by whole-genome DNA microarray. Science284: 1520–1523. 10348738
44. McKinney DM, Southwood S, Hinz D, Oseroff C, Arlehamn CS, et al. (2013) A strategy to determine HLA class II restriction broadly covering the DR, DP, and DQ allelic variants most commonly expressed in the general population. Immunogenetics65: 357–370. doi: 10.1007/s00251-013-0684-y23392739
45. McKinney DM, Fu Z, Le L, Greenbaum JA, Peters B, et al. (2015) Development and validation of a sample sparing strategy for HLA typing utilizing next generation sequencing. Hum Immunol.
46. Panina-Bordignon P, Tan A, Termijtelen A, Demotz S, Corradin G, et al. (1989) Universally immunogenic T cell epitopes: promiscuous binding to human MHC class II and promiscuous recognition by T cells. Eur J Immunol19: 2237–2242. 2481588
47. Assarsson E, Bui H-H, Sidney J, Zhang Q, Glenn J, et al. (2008) Immunomic Analysis of the Repertoire of T-Cell Specificities for Influenza A Virus in Humans. J Virol82: 12241–12251. doi: 10.1128/JVI.01563-0818842709
48. Sette A, Vitiello A, Reherman B, Fowler P, Nayersina R, et al. (1994) The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J Immunol153: 5586–5592. 7527444
49. Vita R, Overton JA, Greenbaum JA, Ponomarenko J, Clark JD, et al. (2015) The immune epitope database (IEDB) 3.0. Nucleic Acids Res43: D405–412. doi: 10.1093/nar/gku93825300482
50. Carrasco Pro S, Sidney J, Paul S, Lindestam Arlehamn C, Weiskopf D, et al. (2015) Automatic Generation of Validated Specific Epitope Sets. Journal of Immunology Research2015: 11.
51. Oseroff C, Sidney J, Vita R, Tripple V, McKinney DM, et al. (2012) T cell responses to known allergen proteins are differently polarized and account for a variable fraction of total response to allergen extracts. Journal of immunology189: 1800–1811.
52. Shams H, Klucar P, Weis SE, Lalvani A, Moonan PK, et al. (2004) Characterization of a Mycobacterium tuberculosis Peptide That Is Recognized by Human CD4+ and CD8+ T Cells in the Context of Multiple HLA Alleles. J Immunol173: 1966–1977. 15265931
53. Mustafa AS, (2014) Characterization of a cross-reactive, immunodominant and HLA-promiscuous epitope of Mycobacterium tuberculosis-specific major antigenic protein PPE68. PLoS One9: e103679. doi: 10.1371/journal.pone.010367925136958
54. Caccamo N, Barera A, Sano CD, Meraviglia S, Ivanyi J, et al. (2003) Cytokine profile, HLA restriction and TCR sequence analysis of human CD4+ T clones specific for an immunodominant epitope of Mycobacterium tuberculosis 16-kDa protein. Clinical & Experimental Immunology133: 260–266.
55. Wilkinson KA, Wilkinson RJ, Pathan A, Ewer K, Prakash M, et al. (2005) Ex vivo characterization of early secretory antigenic target 6-specific T cells at sites of active disease in pleural tuberculosis. Clin Infect Dis40: 184–187. 15614710
56. Greenbaum J, Sidney J, Chung J, Brander C, Peters B, et al. (2011) Functional classification of class II human leukocyte antigen (HLA) molecules reveals seven different supertypes and a surprising degree of repertoire sharing across supertypes. Immunogenetics63: 325–335. doi: 10.1007/s00251-011-0513-021305276
57. Sidney J, Steen A, Moore C, Ngo S, Chung J, et al. (2010) Divergent Motifs but Overlapping Binding Repertoires of Six HLA-DQ Molecules Frequently Expressed in the Worldwide Human Population. The Journal of Immunology185: 4189–4198. doi: 10.4049/jimmunol.100100620810981
58. Sidney J, Steen A, Moore C, Ngo S, Chung J, et al. (2010) Five HLA-DP Molecules Frequently Expressed in the Worldwide Human Population Share a Common HLA Supertypic Binding Specificity. The Journal of Immunology184: 2492–2503. doi: 10.4049/jimmunol.090365520139279
59. Nepom GT, (2012) MHC class II tetramers. J Immunol188: 2477–2482. doi: 10.4049/jimmunol.110239822389204
60. Davis MM, Altman JD, Newell EW, (2011) Interrogating the repertoire: broadening the scope of peptide-MHC multimer analysis. Nat Rev Immunol11: 551–558. doi: 10.1038/nri302021760610
61. Newell EW, (2013) Higher throughput methods of identifying T cell epitopes for studying outcomes of altered antigen processing and presentation. Front Immunol4: 430. doi: 10.3389/fimmu.2013.0043024367368
62. Newell EW, Davis MM, (2014) Beyond model antigens: high-dimensional methods for the analysis of antigen-specific T cells. Nat Biotechnol32: 149–157. doi: 10.1038/nbt.278324441473
63. Newell EW, Sigal N, Nair N, Kidd BA, Greenberg HB, et al. (2013) Combinatorial tetramer staining and mass cytometry analysis facilitate T-cell epitope mapping and characterization. Nat Biotechnol31: 623–629. doi: 10.1038/nbt.259323748502
64. Baena A, Porcelli SA, (2009) Evasion and subversion of antigen presentation by Mycobacterium tuberculosis. Tissue Antigens74: 189–204. doi: 10.1111/j.1399-0039.2009.01301.x19563525
65. Lindestam Arlehamn CS, Paul S, Mele F, Huang C, Greenbaum JA, et al. (2015) Immunological consequences of intragenus conservation of Mycobacterium tuberculosis T-cell epitopes. Proc Natl Acad Sci U S A112: E147–155. doi: 10.1073/pnas.141653711225548174
66. Carpenter C, Sidney J, Kolla R, Nayak K, Tomiyama H, et al. (2015) A side-by-side comparison of T cell reactivity to fifty-nine Mycobacterium tuberculosis antigens in diverse populations from five continents. Tuberculosis (Edinb).
67. Mothe BR, Lindestam Arlehamn CS, Dow C, Dillon MB, Wiseman RW, et al. (2015) The TB-specific CD4(+) T cell immune repertoire in both cynomolgus and rhesus macaques largely overlap with humans. Tuberculosis (Edinb)95: 722–735.
68. Karp CL, Wilson CB, Stuart LM, (2015) Tuberculosis vaccines: barriers and prospects on the quest for a transformative tool. Immunol Rev264: 363–381. doi: 10.1111/imr.1227025703572
69. Pai M, Denkinger CM, Kik SV, Rangaka MX, Zwerling A, et al. (2014) Gamma interferon release assays for detection of Mycobacterium tuberculosis infection. Clin Microbiol Rev27: 3–20. doi: 10.1128/CMR.00034-1324396134
70. Mahomed H, Hawkridge T, Verver S, Abrahams D, Geiter L, et al. (2011) The Tuberculin Skin Test versus QuantiFERON TB Gold® in Predicting Tuberculosis Disease in an Adolescent Cohort Study in South Africa. PLoS ONE6: e17984. doi: 10.1371/journal.pone.001798421479236
71. Mahomed H, Hawkridge T, Verver S, Geiter L, Hatherill M, et al. (2011) Predictive factors for latent tuberculosis infection among adolescents in a high-burden area in South Africa. Int J Tuberc Lung Dis15: 331–336. 21333099
72. Mahomed H, Ehrlich R, Hawkridge T, Hatherill M, Geiter L, et al. (2013) TB incidence in an adolescent cohort in South Africa. PLoS One8: e59652. doi: 10.1371/journal.pone.005965223533639
73. Gonzalez-Galarza FF, Takeshita LY, Santos EJ, Kempson F, Maia MH, et al. (2015) Allele frequency net 2015 update: new features for HLA epitopes, KIR and disease and HLA adverse drug reaction associations. Nucleic Acids Res43: D784–788. doi: 10.1093/nar/gku116625414323