Skip to main content
SpringerLink
Log in

A Systems Approach to Understand Antigen Presentation and the Immune Response

  • Protocol
  • First Online:
Proteomics in Systems Biology

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1394))

Abstract

The mammalian immune system has evolved to respond to pathogenic, environmental, and cellular changes in order to maintain the health of the host. These responses include the comparatively primitive innate immune response, which represents a rapid and relatively nonspecific reaction to challenge by pathogens and the more complex cellular adaptive immune response. This adaptive response evolves with the pathogenic challenge, involves the cross talk of several cell types, and is highly specific to the pathogen due to the liberation of peptide antigens and their presentation on the surface of affected cells. Together these two forms of immunity provide a surveillance mechanism for the system-wide scrutiny of cellular function, environment, and health. As such the immune system is best understood at a systems biology level, and studies that combine gene expression, protein expression, and liberation of peptides for antigen presentation can be combined to provide a detailed understanding of immunity. This chapter details our experience in identifying peptide antigens and combining this information with more traditional proteomics approaches to understand the generation of immune responses on a holistic level.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  1. Madden DR (1995) The three-dimensional structure of peptide-MHC complexes. Annu Rev Immunol 15:587–622

    Article  Google Scholar 

  2. Stern LJ, Brown JH, Jardetzky TS et al (1994) Crystal structure of the human class II MHC protein HLA-DR1 complexed with an influenza virus peptide. Nature 368(6468):215–221

    Article  CAS  PubMed  Google Scholar 

  3. Fremont DH, Hendrickson WA, Marrack P et al (1996) Structures of an MHC class II molecule with covalently bound single peptides. Science 272(5264):1001–1004

    Article  CAS  PubMed  Google Scholar 

  4. Garcia KC, Teyton L, Wilson IA (1999) Structural basis of T cell recognition. Annu Rev Immunol 17:369–397

    Article  CAS  PubMed  Google Scholar 

  5. Falk K, Rötzschke O, Deres K et al (1991) Identification of naturally processed viral nonapeptides allows their quantification in infected cells and suggests an allele-specific T cell epitope forecast. J Exp Med 174:425–434

    Article  CAS  PubMed  Google Scholar 

  6. Sijts AJ, Neisig A, Neefjes J et al (1996) Two Listeria monocytogenes CTL epitopes are processed from the same antigen with different efficiencies. J Immunol 156(2):683–692

    CAS  PubMed  Google Scholar 

  7. Rotzschke O, Falk K, Deres K et al (1990) Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells. Nature 348(6298):252–254

    Article  CAS  PubMed  Google Scholar 

  8. Storkus WJ, Zeh HJ, Maeurer MJ et al (1993) Identification of human melanoma peptides recognized by class I restricted tumor infiltrating T lymphocytes. J Immunol 151(7):3719–3727

    CAS  PubMed  Google Scholar 

  9. Storkus WJ, Zeh HJ, Salter RD et al (1993) Identification of T-cell epitopes: rapid isolation of class I-presented peptides from viable cells by mild acid elution. J Immunother 14(2):94–103

    Article  CAS  Google Scholar 

  10. Falk K, Rötzschke O, Stevanovic S et al (1991) Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 351:290–296

    Article  CAS  PubMed  Google Scholar 

  11. Rammensee HG, Falk K, Rotzschke O (1993) Peptides naturally presented by MHC class I molecules. Annu Rev Immunol 11:213–244

    Article  CAS  PubMed  Google Scholar 

  12. Scull KE, Dudek NL, Corbett AJ et al (2012) Secreted HLA recapitulates the immunopeptidome and allows in-depth coverage of HLA A*02:01 ligands. Mol Immunol 51(2):136–142

    Article  CAS  PubMed  Google Scholar 

  13. Illing PT, Vivian JP, Dudek NL et al (2012) Immune self-reactivity triggered by drug-modified HLA-peptide repertoire. Nature 486(7404):554–558

    CAS  PubMed  Google Scholar 

  14. Dudek NL, Tan CT, Gorasia DG et al (2012) Constitutive and inflammatory immunopeptidome of pancreatic beta-cells. Diabetes 61(11):3018–3025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Urban RG, Chicz RM, Lane WS et al (1994) A subset of HLA-B27 molecules contains peptides much longer than nonamers. Proc Natl Acad Sci U S A 91(4):1534–1538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Purcell AW, Kelly AJ, Peh CA et al (2000) Endogenous and exogenous factors contributing to the surface expression of HLA B27 on mutant APC. Hum Immunol 61(2):120–130

    Article  CAS  PubMed  Google Scholar 

  17. Storkus WJ, Howell DN, Salter RD et al (1987) NK susceptibility varies inversely with target cell class I HLA antigen expression. J Immunol 138(6):1657–1659

    CAS  PubMed  Google Scholar 

  18. Macdonald WA, Purcell AW, Mifsud NA et al (2003) A naturally selected dimorphism within the HLA-B44 supertype alters class I structure, peptide repertoire, and T cell recognition. J Exp Med 198(5):679–691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Zernich D, Purcell AW, Macdonald WA et al (2004) Natural HLA class I polymorphism controls the pathway of antigen presentation and susceptibility to viral evasion. J Exp Med 200(1):13–24

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Scally SW, Petersen J, Law SC et al (2013) A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis. J Exp Med 210(12):2569–2582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ringrose JH, Yard BA, Muijsers A et al (1996) Comparison of peptides eluted from the groove of HLA-B27 from Salmonella infected and non-infected cells. Clin Rheumatol 15 Suppl 1:74–78

    Google Scholar 

  22. van Els CA, Herberts CA, van der Heeft E et al (2000) A single naturally processed measles virus peptide fully dominates the HLA-A*0201-associated peptide display and is mutated at its anchor position in persistent viral strains. Eur J Immunol 30(4):1172–1181

    Article  PubMed  Google Scholar 

  23. Nepom BS, Nepom GT, Coleman M et al (1996) Critical contribution of beta chain residue 57 in peptide binding ability of both HLA-DR and -DQ molecules. Proc Natl Acad Sci U S A 93(14):7202–7206

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Lampson LA, Levy R (1980) Two populations of Ia-like molecules on a human B cell line. J Immunol 125(1):293–299

    CAS  PubMed  Google Scholar 

  25. Gorga JC, Knudsen PJ, Foran JA et al (1986) Immunochemically purified DR antigens in liposomes stimulate xenogeneic cytolytic T cells in secondary in vitro cultures. Cell Immunol 103(1):160–173

    Article  CAS  PubMed  Google Scholar 

  26. Watson AJ, DeMars R, Trowbridge IS et al (1983) Detection of a novel human class II HLA antigen. Nature 304(5924):358–361

    Article  CAS  PubMed  Google Scholar 

  27. Parham P, Brodsky FM (1981) Partial purification and some properties of BB7.2. A cytotoxic monoclonal antibody with specificity for HLA-A2 and a variant of HLA-A28. Hum Immunol 3(4):277–299

    Article  CAS  PubMed  Google Scholar 

  28. Ellis SA, Taylor C, McMichael A (1982) Recognition of HLA-B27 and related antigen by a monoclonal antibody. Hum Immunol 5(1):49–59

    Article  CAS  PubMed  Google Scholar 

  29. Schittenhelm RB, Dudek NL, Croft NP et al (2014) A comprehensive analysis of constitutive naturally processed and presented HLA-C*04:01 (Cw4)-specific peptides. Tissue Antigens 83(3):174–179

    Article  CAS  PubMed  Google Scholar 

  30. Braud VM, Allan DS, Wilson D et al (1998) TAP- and tapasin-dependent HLA-E surface expression correlates with the binding of an MHC class I leader peptide. Curr Biol 8(1):1–10

    Article  CAS  PubMed  Google Scholar 

  31. Thomas R, Apps R, Qi Y et al (2009) HLA-C cell surface expression and control of HIV/AIDS correlate with a variant upstream of HLA-C. Nat Genet 41(12):1290–1294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Hammerling GJ, Rusch E, Tada N et al (1982) Localization of allodeterminants on H-2Kb antigens determined with monoclonal antibodies and H-2 mutant mice. Proc Natl Acad Sci U S A 79(15):4737–4741

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Straus DS, Stroynowski I, Schiffer SG et al (1985) Expression of hybrid class I genes of the major histocompatibility complex in mouse L cells. Proc Natl Acad Sci U S A 82(18):6245–6249

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Ozato K, Sachs DH (1981) Monoclonal antibodies to mouse MHC antigens. III. Hybridoma antibodies reacting to antigens of the H-2b haplotype reveal genetic control of isotype expression. J Immunol 126(1):317–321

    CAS  PubMed  Google Scholar 

  35. Kappler JW, Skidmore B, White J et al (1981) Antigen-inducible, H-2-restricted, interleukin-2-producing T cell hybridomas. Lack of independent antigen and H-2 recognition. J Exp Med 153(5):1198–1214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Janeway CA Jr, Conrad PJ, Lerner EA et al (1984) Monoclonal antibodies specific for Ia glycoproteins raised by immunization with activated T cells: possible role of T cellbound Ia antigens as targets of immunoregulatory T cells. J Immunol 132(2):662–667

    PubMed  Google Scholar 

  37. Oi VT, Jones PP, Goding JW et al (1978) Properties of monoclonal antibodies to mouse Ig allotypes, H-2, and Ia antigens. Curr Top Microbiol Immunol 81:115–120

    CAS  PubMed  Google Scholar 

  38. Croft NP, Smith SA, Wong YC et al (2013) Kinetics of antigen expression and epitope presentation during virus infection. PLoS Pathog 9(1), e1003129

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Tan CT, Croft NP, Dudek NL et al (2011) Direct quantitation of MHC-bound peptide epitopes by selected reaction monitoring. Proteomics 11(11):2336–2340

    Article  CAS  PubMed  Google Scholar 

  40. Wisniewski JR, Zougman A, Nagaraj N et al (2009) Universal sample preparation method for proteome analysis. Nat Methods 6(5):359–362. doi:10.1038/nmeth.1322

    Article  CAS  PubMed  Google Scholar 

  41. Lange V, Picotti P, Domon B et al (2008) Selected reaction monitoring for quantitative proteomics: a tutorial. Mol Syst Biol 4:222

    Article  PubMed  PubMed Central  Google Scholar 

  42. Edwards PA, Smith CM, Neville AM et al (1982) A human-hybridoma system based on a fast-growing mutant of the ARH-77 plasma cell leukemia-derived line. Eur J Immunol 12(8):641–648

    Article  CAS  PubMed  Google Scholar 

  43. Alexander J, Payne JA, Murray R et al (1989) Differential transport requirements of HLA and H-2 class I glycoproteins. Immunogenetics 29(6):380–388

    Article  CAS  PubMed  Google Scholar 

  44. Nelson CA, Roof RW, McCourt DW et al (1992) Identification of the naturally processed form of hen egg white lysozyme bound to the murine major histocompatibility complex class II molecule I-Ak. Proc Natl Acad Sci U S A 89(16):7380–7383

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Escher C, Reiter L, MacLean B et al (2012) Using iRT, a normalized retention time for more targeted measurement of peptides. Proteomics 12(8):1111–1121

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, VIC, 3800, Australia

    Nadine L. Dudek, Nathan P. Croft, Ralf B. Schittenhelm, Sri H. Ramarathinam & Anthony W. Purcell

  2. The Department of Biochemistry and Molecular Biology, The Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, VIC, 3010, Australia

    Anthony W. Purcell

Authors
  1. Nadine L. Dudek
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nathan P. Croft
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ralf B. Schittenhelm
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sri H. Ramarathinam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Anthony W. Purcell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anthony W. Purcell .

Editor information

Editors and Affiliations

  1. University of Regensburg Institute of Functional Genomics, Regensburg, Germany

    Jörg Reinders

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Dudek, N.L., Croft, N.P., Schittenhelm, R.B., Ramarathinam, S.H., Purcell, A.W. (2016). A Systems Approach to Understand Antigen Presentation and the Immune Response. In: Reinders, J. (eds) Proteomics in Systems Biology. Methods in Molecular Biology, vol 1394. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3341-9_14

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-3341-9_14

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-3339-6

  • Online ISBN: 978-1-4939-3341-9

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation