Analysis of Major Histocompatibility Complex (MHC) Immunopeptidomes Using Mass Spectrometry*

The myriad of peptides presented at the cell surface by class I and class II major histocompatibility complex (MHC) molecules are referred to as the immunopeptidome and are of great importance for basic and translational science. For basic science, the immunopeptidome is a critical component for understanding the immune system; for translational science, exact knowledge of the immunopeptidome can directly fuel and guide the development of next-generation vaccines and immunotherapies against autoimmunity, infectious diseases, and cancers. In this mini-review, we summarize established isolation techniques as well as emerging mass spectrometry-based platforms (i.e. SWATH-MS) to identify and quantify MHC-associated peptides. We also highlight selected biological applications and discuss important current technical limitations that need to be solved to accelerate the development of this field.

[1]  John D. Venable,et al.  Automated approach for quantitative analysis of complex peptide mixtures from tandem mass spectra , 2004, Nature Methods.

[2]  Albert J R Heck,et al.  Toward full peptide sequence coverage by dual fragmentation combining electron-transfer and higher-energy collision dissociation tandem mass spectrometry. , 2012, Analytical chemistry.

[3]  J. Couzin.  Small RNAs Make Big Splash , 2002, Science.

[4]  Peter A van Veelen,et al.  Accurate quantitation of MHC-bound peptides by application of isotopically labeled peptide MHC complexes. , 2014, Journal of proteomics.

[5]  Taku Kambayashi,et al.  Atypical MHC class II-expressing antigen-presenting cells: can anything replace a dendritic cell? , 2014, Nature Reviews Immunology.

[6]  Jeroen Krijgsveld,et al.  Ultrasensitive proteome analysis using paramagnetic bead technology , 2014, Molecular systems biology.

[7]  Alessandro Sette,et al.  An open-source computational and data resource to analyze digital maps of immunopeptidomes , 2015, eLife.

[8]  N. Shastri,et al.  Producing nature's gene-chips: the generation of peptides for display by MHC class I molecules. , 2002, Annual review of immunology.

[9]  Ruedi Aebersold,et al.  Mass spectrometric protein maps for biomarker discovery and clinical research , 2013, Expert review of molecular diagnostics.

[10]  H R Bergen,et al.  Mass Spectrometry and Peptide‐based Vaccine Development , 2007, Clinical pharmacology and therapeutics.

[11]  Joachim L Schultze,et al.  Teaching 'big data' analysis to young immunologists , 2015, Nature Immunology.

[12]  V. Marx.  Targeted proteomics , 2013, Nature Methods.

[13]  Donald Kennedy,et al.  Breakthrough of the Year , 2007, Science.

[14]  James McCluskey,et al.  HLA Peptide Length Preferences Control CD8+ T Cell Responses , 2013, The Journal of Immunology.

[15]  J. Yewdell,et al.  Mining the plasma immunopeptidome for cancer peptides as biomarkers and beyond , 2010, Proceedings of the National Academy of Sciences.

[16]  Arie Admon,et al.  The Human Immunopeptidome Project, a Suggestion for yet another Postgenome Next Big Thing , 2011, Molecular & Cellular Proteomics.

[17]  Ton N Schumacher,et al.  Alloreactive cytotoxic T cells provide means to decipher the immunopeptidome and reveal a plethora of tumor-associated self-epitopes , 2013, Proceedings of the National Academy of Sciences.

[18]  Jennifer Couzin-Frankel,et al.  Breakthrough of the year 2013. Cancer immunotherapy. , 2013, Science.

[19]  H. Rammensee,et al.  Characterization of naturally occurring minor histocompatibility peptides including H-4 and H-Y. , 1990, Science.

[20]  Ming Zhou,et al.  Relative Expression Levels of the HLA Class-I Proteins in Normal and HIV-Infected Cells , 2015, The Journal of Immunology.

[21]  Kie Kasuga,et al.  Comprehensive analysis of MHC ligands in clinical material by immunoaffinity-mass spectrometry. , 2013, Methods in molecular biology.

[22]  Birgit Schilling,et al.  Repeatability and reproducibility in proteomic identifications by liquid chromatography-tandem mass spectrometry. , 2010, Journal of proteome research.

[23]  Peter Parham,et al.  Part 5 – HLA-F , 2000 .

[24]  Nina Hillen,et al.  Contribution of mass spectrometry-based proteomics to immunology , 2006, Expert review of proteomics.

[25]  Lennart Martens,et al.  Machine learning applications in proteomics research: How the past can boost the future , 2014, Proteomics.

[26]  Christian Brander,et al.  Direct Interrogation of Viral Peptides Presented by the Class I HLA of HIV-Infected T Cells , 2014, Journal of Virology.

[27]  N. Croft,et al.  A comprehensive analysis of peptides presented by HLA-A1. , 2015, Tissue antigens.

[28]  Daniel López,et al.  The Viral Transcription Group Determines the HLA Class I Cellular Immune Response Against Human Respiratory Syncytial Virus* , 2015, Molecular & Cellular Proteomics.

[29]  Sébastien Lemieux,et al.  Deletion of Immunoproteasome Subunits Imprints on the Transcriptome and Has a Broad Impact on Peptides Presented by Major Histocompatibility Complex I molecules* , 2010, Molecular & Cellular Proteomics.

[30]  P. Roche,et al.  The ins and outs of MHC class II-mediated antigen processing and presentation , 2015, Nature Reviews Immunology.

[31]  Susan E Abbatiello,et al.  Effect of collision energy optimization on the measurement of peptides by selected reaction monitoring (SRM) mass spectrometry. , 2010, Analytical chemistry.

[32]  Jing Chen,et al.  Glycoproteomic Analysis of Prostate Cancer Tissues by SWATH Mass Spectrometry Discovers N-acylethanolamine Acid Amidase and Protein Tyrosine Kinase 7 as Signatures for Tumor Aggressiveness , 2014, Molecular & Cellular Proteomics.

[33]  Ruedi Aebersold,et al.  Automated selected reaction monitoring data analysis workflow for large-scale targeted proteomic studies , 2013, Nature Protocols.

[34]  D. Lake,et al.  Proteomic identification of an MHC-binding peptidome from pancreas and breast cancer cell lines. , 2009, Molecular immunology.

[35]  Jan O. Korbel,et al.  Data analysis: Create a cloud commons , 2015, Nature.

[36]  D. Keskin,et al.  A Conserved E7-derived Cytotoxic T Lymphocyte Epitope Expressed on Human Papillomavirus 16-transformed HLA-A2+ Epithelial Cancers , 2010, The Journal of Biological Chemistry.

[37]  M. Heemskerk,et al.  Identification of Biological Relevant Minor Histocompatibility Antigens within the B-lymphocyte–Derived HLA-Ligandome Using a Reverse Immunology Approach , 2015, Clinical Cancer Research.

[38]  J. Yates,et al.  A model for random sampling and estimation of relative protein abundance in shotgun proteomics. , 2004, Analytical chemistry.

[39]  Pei Wang,et al.  Demonstrating the feasibility of large-scale development of standardized assays to quantify human proteins , 2013, Nature Methods.

[40]  Olga Vitek,et al.  Extending the limits of quantitative proteome profiling with data-independent acquisition , 2015 .

[41]  D. Cole,et al.  The ultimate mix and match: making sense of HLA alleles and peptide repertoires , 2015, Immunology and cell biology.

[42]  S Walz,et al.  Mapping the HLA ligandome landscape of acute myeloid leukemia: a targeted approach toward peptide-based immunotherapy , 2014, Leukemia.

[43]  Chih-Chiang Tsou,et al.  DIA-Umpire: comprehensive computational framework for data-independent acquisition proteomics , 2015, Nature Methods.

[44]  Magdalini Moutaftsi,et al.  A consensus epitope prediction approach identifies the breadth of murine TCD8+-cell responses to vaccinia virus , 2006, Nature Biotechnology.

[45]  M. A. Saper,et al.  Specificity pockets for the side chains of peptide antigens in HLA-Aw68 , 1990, Nature.

[46]  Hans-Georg Rammensee,et al.  Isolation and analysis of naturally processed viral peptides as recognized by cytotoxic T cells , 1990, Nature.

[47]  Anthony W. Purcell,et al.  The Cellular Redox Environment Alters Antigen Presentation* , 2014, The Journal of Biological Chemistry.

[48]  Derek J. Bailey,et al.  Parallel Reaction Monitoring for High Resolution and High Mass Accuracy Quantitative, Targeted Proteomics* , 2012, Molecular & Cellular Proteomics.

[49]  D. Crockett,et al.  Utility of characteristic QTOF MS/MS fragmentation for MHC class I peptides. , 2011, Journal of proteome research.

[50]  James McCluskey,et al.  The peptide length specificity of some HLA class I alleles is very broad and includes peptides of up to 25 amino acids in length. , 2009, Molecular immunology.

[51]  Ruedi Aebersold,et al.  Quantitative variability of 342 plasma proteins in a human twin population , 2015 .

[52]  Albert J R Heck,et al.  Expanding the detectable HLA peptide repertoire using electron-transfer/higher-energy collision dissociation (EThcD) , 2014, Proceedings of the National Academy of Sciences.

[53]  P. Cresswell,et al.  Papain-solubilized HL-A antigens from cultured human lymphocytes contain two peptide fragments. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[54]  M. Mann,et al.  More than 100,000 detectable peptide species elute in single shotgun proteomics runs but the majority is inaccessible to data-dependent LC-MS/MS. , 2011, Journal of proteome research.

[55]  P. Sharma,et al.  The future of immune checkpoint therapy , 2015, Science.

[56]  Morten Nielsen,et al.  NetMHCcons: a consensus method for the major histocompatibility complex class I predictions , 2011, Immunogenetics.

[57]  Hans-Georg Rammensee,et al.  Exploiting the glioblastoma peptidome to discover novel tumour-associated antigens for immunotherapy. , 2012, Brain : a journal of neurology.

[58]  Ton N Schumacher,et al.  Biomarkers in cancer immunotherapy. , 2015, Cancer cell.

[59]  E. Mardis,et al.  A dendritic cell vaccine increases the breadth and diversity of melanoma neoantigen-specific T cells , 2015, Science.

[60]  C. Lynch.  Big data: How do your data grow? , 2008, Nature.

[61]  Nina Hillen,et al.  Exploring the MHC-peptide matrix of central tolerance in the human thymus , 2013, Nature Communications.

[62]  Eric W. Deutsch,et al.  A repository of assays to quantify 10,000 human proteins by SWATH-MS , 2014, Scientific Data.

[63]  Ludovic C. Gillet,et al.  Rapid mass spectrometric conversion of tissue biopsy samples into permanent quantitative digital proteome maps , 2015, Nature Medicine.

[64]  Jörn Dengjel,et al.  Mass spectrometry analysis and quantitation of peptides presented on the MHC II molecules of mouse spleen dendritic cells. , 2011, Journal of proteome research.

[65]  Kai Pong Law,et al.  Recent advances in mass spectrometry: data independent analysis and hyper reaction monitoring , 2013, Expert review of proteomics.

[66]  Hans-Georg Rammensee,et al.  Cellular peptide composition governed by major histocompatibility complex class I molecules , 1990, Nature.

[67]  Adele Bourmaud,et al.  Technical considerations for large-scale parallel reaction monitoring analysis. , 2014, Journal of proteomics.

[68]  Martin von Bergen,et al.  Comparison of targeted peptide quantification assays for reductive dehalogenases by selective reaction monitoring (SRM) and precursor reaction monitoring (PRM) , 2013, Analytical and Bioanalytical Chemistry.

[69]  Greg J. Towers,et al.  HLA-Specific Intracellular Epitope Processing Shapes an Immunodominance Pattern for HLA-B*57 That Is Distinct from HLA-B*58:01 , 2013, Journal of Virology.

[70]  Karl Mechtler,et al.  Unambiguous Phosphosite Localization using Electron-Transfer/Higher-Energy Collision Dissociation (EThcD) , 2013, Journal of proteome research.

[71]  Wilfried Bardet,et al.  Identification of breast cancer peptide epitopes presented by HLA-A*0201. , 2008, Journal of proteome research.

[72]  Hamid Mirzaei,et al.  Rapid optimization of MRM-MS instrument parameters by subtle alteration of precursor and product m/z targets. , 2009, Journal of proteome research.

[73]  A. Purcell,et al.  Revisiting the Arthritogenic Peptide Theory: Quantitative Not Qualitative Changes in the Peptide Repertoire of HLA–B27 Allotypes , 2015, Arthritis & rheumatology.

[74]  S. Stevanović,et al.  Insights into MHC class I antigen processing gained from large-scale analysis of class I ligands , 2011, Cellular and Molecular Life Sciences.

[75]  Morten Nielsen,et al.  A Community Resource Benchmarking Predictions of Peptide Binding to MHC-I Molecules , 2006, PLoS Comput. Biol..

[76]  J. Leunissen,et al.  The Human Leukocyte Antigen–presented Ligandome of B Lymphocytes* , 2013, Molecular & Cellular Proteomics.

[77]  Maxim N. Artyomov,et al.  Checkpoint Blockade Cancer Immunotherapy Targets Tumour-Specific Mutant Antigens , 2014, Nature.

[78]  Ilan Beer,et al.  The Effect of Proteasome Inhibition on the Generation of the Human Leukocyte Antigen (HLA) Peptidome* , 2013, Molecular & Cellular Proteomics.

[79]  R. Paroni,et al.  Quantitative cytometry of MHC class I digestion from living cells. , 1997, Cytometry.

[80]  Bruno Domon,et al.  Advances in high‐resolution accurate mass spectrometry application to targeted proteomics , 2015, Proteomics.

[81]  L. Rohrer,et al.  Attack by Peptide-Specific CTL Protect Vascular Endothelial Cells from an Two Preferentially Expressed Proteins , 2012 .

[82]  Ruedi Aebersold,et al.  Proteomics meets the scientific method , 2013, Nature Methods.

[83]  Juan Pablo Albar,et al.  Increased Diversity of the HLA-B40 Ligandome by the Presentation of Peptides Phosphorylated at Their Main Anchor Residue* , 2013, Molecular & Cellular Proteomics.

[84]  H. Rammensee,et al.  SYFPEITHI: database for MHC ligands and peptide motifs , 1999, Immunogenetics.

[85]  J. Drijfhout,et al.  Discovery of T Cell Epitopes Implementing HLA-Peptidomics into a Reverse Immunology Approach , 2013, The Journal of Immunology.

[86]  M. A. Saper,et al.  The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens , 1987, Nature.

[87]  Hiroaki Tanaka,et al.  Multipeptide immune response to cancer vaccine IMA901 after single-dose cyclophosphamide associates with longer patient survival , 2012, Nature Medicine.

[88]  Sébastien Lemieux,et al.  The MHC I immunopeptidome conveys to the cell surface an integrative view of cellular regulation , 2011, Molecular systems biology.

[89]  S. Nathenson,et al.  Isolation of an endogenously processed immunodominant viral peptide from the class I H–2Kb molecule , 1990, Nature.

[90]  Ruedi Aebersold,et al.  SnapShot: Mass Spectrometry for Protein and Proteome Analyses , 2013, Cell.

[91]  Brendan MacLean,et al.  Bioinformatics Applications Note Gene Expression Skyline: an Open Source Document Editor for Creating and Analyzing Targeted Proteomics Experiments , 2022 .

[92]  Ilan Beer,et al.  The HLA-B*2705 peptidome. , 2010, Arthritis and rheumatism.

[93]  Vasso Apostolopoulos,et al.  Non-canonical anchor motif peptides bound to MHC class I induce cellular responses. , 2009, Molecular immunology.

[94]  Pierre Thibault,et al.  Efficient sample processing for proteomics applications—Are we there yet? , 2014, Molecular systems biology.

[95]  R. Aebersold,et al.  Selected reaction monitoring–based proteomics: workflows, potential, pitfalls and future directions , 2012, Nature Methods.

[96]  D. Goodlett,et al.  Multiplexed and data-independent tandem mass spectrometry for global proteome profiling. , 2014, Mass spectrometry reviews.

[97]  S. Stevanović,et al.  Biochemical large-scale identification of MHC class I ligands. , 2013, Methods in molecular biology.

[98]  Arie Admon,et al.  The nature and extent of contributions by defective ribosome products to the HLA peptidome , 2014, Proceedings of the National Academy of Sciences.

[99]  Ludovic C. Gillet,et al.  Quantifying protein interaction dynamics by SWATH mass spectrometry: application to the 14-3-3 system , 2013, Nature Methods.

[100]  Bruno Domon,et al.  Selectivity of LC-MS/MS analysis: implication for proteomics experiments. , 2013, Journal of proteomics.

[101]  G. Jarvik,et al.  Parallel reaction monitoring (PRM) and selected reaction monitoring (SRM) exhibit comparable linearity, dynamic range and precision for targeted quantitative HDL proteomics. , 2015, Journal of proteomics.

[102]  Hans-Georg Rammensee,et al.  HLA ligandome analysis identifies the underlying specificities of spontaneous antileukemia immune responses in chronic lymphocytic leukemia (CLL) , 2014, Proceedings of the National Academy of Sciences.

[103]  M. Lotze,et al.  Identification of T-cell epitopes: rapid isolation of class I-presented peptides from viable cells by mild acid elution. , 1993, Journal of immunotherapy with emphasis on tumor immunology : official journal of the Society for Biological Therapy.

[104]  Stefan Tenzer,et al.  Biomedical applications of ion mobility-enhanced data-independent acquisition-based label-free quantitative proteomics , 2014, Expert review of proteomics.

[105]  R. Aebersold,et al.  Mass spectrometry-based proteomics , 2003, Nature.

[106]  Ilan Beer,et al.  The Turnover Kinetics of Major Histocompatibility Complex Peptides of Human Cancer Cells* , 2006, Molecular & Cellular Proteomics.

[107]  P. A. Peterson,et al.  Highly purified papain-solubilized HL-A antigens contain beta2-microglobulin. , 1974, Proceedings of the National Academy of Sciences of the United States of America.

[108]  Elisa Pappalardo,et al.  Early Kinetics of the HLA Class I-Associated Peptidome of MVA.HIVconsv-Infected Cells , 2015, Journal of Virology.

[109]  Rajiv Khanna,et al.  Preferential binding of unusually long peptides to MHC class I and its influence on the selection of target peptides for T cell recognition. , 2008, Molecular immunology.

[110]  Ruedi Aebersold,et al.  High-throughput generation of selected reaction-monitoring assays for proteins and proteomes , 2010, Nature Methods.

[111]  Volker Brass,et al.  Identification of Naturally Processed Hepatitis C Virus-Derived Major Histocompatibility Complex Class I Ligands , 2012, PloS one.

[112]  Hans-Georg Rammensee,et al.  Distorted Relation between mRNA Copy Number and Corresponding Major Histocompatibility Complex Ligand Density on the Cell Surface*S , 2007, Molecular & Cellular Proteomics.

[113]  R. Aebersold,et al.  Selected reaction monitoring for quantitative proteomics: a tutorial , 2008, Molecular systems biology.

[114]  E. Caron,et al.  The MHC class I peptide repertoire is molded by the transcriptome , 2008, The Journal of experimental medicine.

[115]  Ben C. Collins,et al.  OpenSWATH enables automated, targeted analysis of data-independent acquisition MS data , 2014, Nature Biotechnology.

[116]  Kevin Camphausen,et al.  Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy , 2006 .

[117]  Peter Cresswell,et al.  Mechanisms of MHC class I‐restricted antigen processing and cross‐presentation , 2005, Immunological reviews.

[118]  P. Boutros,et al.  Onco-proteogenomics: cancer proteomics joins forces with genomics , 2014, Nature Methods.

[119]  Anthony W. Purcell,et al.  Constitutive and Inflammatory Immunopeptidome of Pancreatic β-Cells , 2012, Diabetes.

[120]  Ilan Beer,et al.  Large-scale analysis of HLA peptides presented by HLA-Cw4 , 2003, Immunogenetics.

[121]  R. Henderson,et al.  Characterization of peptides bound to the class I MHC molecule HLA-A2.1 by mass spectrometry. , 1992, Science.

[122]  Peter Parham,et al.  The HLA FactsBook , 1999 .

[123]  Alessandro Sette,et al.  Discovering naturally processed antigenic determinants that confer protective T cell immunity. , 2013, The Journal of clinical investigation.

[124]  Etienne Caron,et al.  The structure and location of SIMP/STT3B account for its prominent imprint on the MHC I immunopeptidome. , 2005, International immunology.

[125]  Nicholas A Williamson,et al.  Secreted HLA recapitulates the immunopeptidome and allows in-depth coverage of HLA A*02:01 ligands. , 2012, Molecular immunology.

[126]  T. Kindt,et al.  Primary structural: analysis of the transplantation antigens of the murine H-2 major histocompatibility complex. , 1981, Annual review of biochemistry.

[127]  Sébastien Lemieux,et al.  Impact of genomic polymorphisms on the repertoire of human MHC class I-associated peptides , 2014, Nature Communications.

[128]  B. Simons,et al.  Performance characteristics of a new hybrid quadrupole time-of-flight tandem mass spectrometer (TripleTOF 5600). , 2011, Analytical chemistry.

[129]  Brendan MacLean,et al.  Building high-quality assay libraries for targeted analysis of SWATH MS data , 2015, Nature Protocols.

[130]  M. Mann,et al.  Mass Spectrometry-based Proteomics Using Q Exactive, a High-performance Benchtop Quadrupole Orbitrap Mass Spectrometer* , 2011, Molecular & Cellular Proteomics.

[131]  Eric W. Deutsch,et al.  Combining Results of Multiple Search Engines in Proteomics* , 2013, Molecular & Cellular Proteomics.

[132]  R. Aebersold,et al.  mProphet: automated data processing and statistical validation for large-scale SRM experiments , 2011, Nature Methods.

[133]  Anthony W. Purcell,et al.  Kinetics of Antigen Expression and Epitope Presentation during Virus Infection , 2013, PLoS pathogens.

[134]  D. Lauffenburger,et al.  Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks , 2007, Proceedings of the National Academy of Sciences.

[135]  Muthuraman Sathiamurthy,et al.  Toward a Definition of Self: Proteomic Evaluation of the Class I Peptide Repertoire1 , 2004, The Journal of Immunology.

[136]  R. Aebersold,et al.  Mass Spectrometry and Protein Analysis , 2006, Science.

[137]  Ilan Beer,et al.  Soluble plasma HLA peptidome as a potential source for cancer biomarkers , 2010, Proceedings of the National Academy of Sciences.

[138]  T. Schumacher,et al.  Neoantigens in cancer immunotherapy , 2015, Science.

[139]  N. Croft,et al.  Direct quantitation of MHC‐bound peptide epitopes by selected reaction monitoring , 2011, Proteomics.

[140]  L. Jensen,et al.  Mass Spectrometry of Human Leukocyte Antigen Class I Peptidomes Reveals Strong Effects of Protein Abundance and Turnover on Antigen Presentation* , 2015, Molecular & Cellular Proteomics.

[141]  Z. Modrušan,et al.  Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing , 2014, Nature.

[142]  Jennifer G. Abelin,et al.  MHC Class I–Associated Phosphopeptides Are the Targets of Memory-like Immunity in Leukemia , 2013, Science Translational Medicine.

[143]  Ludovic C. Gillet,et al.  Targeted Data Extraction of the MS/MS Spectra Generated by Data-independent Acquisition: A New Concept for Consistent and Accurate Proteome Analysis* , 2012, Molecular & Cellular Proteomics.

[144]  A. Nesvizhskii.  Proteogenomics: concepts, applications and computational strategies , 2014, Nature Methods.

[145]  Steven P Gygi,et al.  Target-decoy search strategy for increased confidence in large-scale protein identifications by mass spectrometry , 2007, Nature Methods.

[146]  Bjoern Peters,et al.  The immune epitope database: a historical retrospective of the first decade , 2012, Immunology.

[147]  William Stafford Noble,et al.  Semi-supervised learning for peptide identification from shotgun proteomics datasets , 2007, Nature Methods.

[148]  Henry H. N. Lam,et al.  A database of mass spectrometric assays for the yeast proteome , 2008, Nature Methods.

[149]  Sébastien Lemieux,et al.  MHC I-associated peptides preferentially derive from transcripts bearing miRNA response elements. , 2012, Blood.

[150]  Ilka Hoof,et al.  Comprehensive Analysis of the Naturally Processed Peptide Repertoire: Differences between HLA-A and B in the Immunopeptidome , 2015, PloS one.

[151]  Jennifer N. Sutton,et al.  Use of selected reaction monitoring mass spectrometry for the detection of specific MHC class I peptide antigens on A3 supertype family members , 2005, Cancer Immunology, Immunotherapy.

[152]  H. Rammensee,et al.  Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules , 1991, Nature.

[153]  Ruedi Aebersold,et al.  Absolute Proteome Composition and Dynamics during Dormancy and Resuscitation of Mycobacterium tuberculosis. , 2015, Cell host & microbe.

[154]  Ruedi Aebersold,et al.  Using data‐independent, high‐resolution mass spectrometry in protein biomarker research: Perspectives and clinical applications , 2015, Proteomics. Clinical applications.

[155]  Ruedi Aebersold,et al.  Conserved Peptide Fragmentation as a Benchmarking Tool for Mass Spectrometers and a Discriminating Feature for Targeted Proteomics* , 2014, Molecular & Cellular Proteomics.

[156]  C. Perreault,et al.  The nature of self for T cells-a systems-level perspective. , 2015, Current opinion in immunology.

[157]  A. Nesvizhskii.  A survey of computational methods and error rate estimation procedures for peptide and protein identification in shotgun proteomics. , 2010, Journal of proteomics.

[158]  Oliver M. Bernhardt,et al.  Reproducible and Consistent Quantification of the Saccharomyces cerevisiae Proteome by SWATH-mass spectrometry* , 2015, Molecular & Cellular Proteomics.

[159]  Daniel B. Martin,et al.  Collision energy optimization of b- and y-ions for multiple reaction monitoring mass spectrometry. , 2011, Journal of proteome research.

[160]  Bernhard Kuster,et al.  DMSO enhances electrospray response, boosting sensitivity of proteomic experiments , 2013, Nature Methods.