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MHC Informatics to Peptide Vaccine Design

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Abstract

The major histocompatibility complex (MHC) genes are highly polymorphic (sequence-level variation) among different ethnic population (Black, Caucasoid, Oriental, Hispanic, mixed race, Pacific Islander, American Indian, and Australian aboriginal). The sequences for MHC genes among the population are known, named, and made available at the IMGT/HLA databases. The current database update consists of more than 18,000 human leukocyte antigen (HLA) alleles as on early 2018. The binding of short peptides (8–20 residues long) to MHC molecules has an important role in T-cell-mediated immune response. The binding prediction of peptides to MHC is challenging due to its sequence polymorphism among ethnic groups. MHC-peptide binding prediction in the design of T-cell epitopes using T-EPITOPE Designer for short peptide vaccine development is discussed. However, it has been suggested that majority of alleles can be covered within few HLA supertypes, where different members of a supertype bind similar peptides, yet exhibiting distinct repertoires. The grouping of HLA alleles into different categories of supertypes has profound use in the understanding of antigenic peptide selection, degeneration, and discrimination during T-cell-mediated immune response. This phenomenon is highly useful in the identification of super antigens specific to several known alleles as vaccine candidates with broad immunity.

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References

  • Altman JD, Moss PA, Goulder PJR et al (1996) Phenotypic analysis of antigen-specific T lymphocytes. Science 274:94–96

    Article  CAS  PubMed  Google Scholar 

  • Altuvia Y, Schueler O, Margalit H (1995) Ranking potential binding peptides to MHC molecules by a computational threading approach. J Mol Biol 249:244–250

    Article  CAS  PubMed  Google Scholar 

  • Altuvia Y, Sette A, Sidney J et al (1997) A structure-based algorithm to predict potential binding peptides to MHC molecules with hydrophobic binding pockets. Hum Immunol 58:1–11

    Article  CAS  PubMed  Google Scholar 

  • Batalia MA, Collins EJ (1997) Peptide binding by class I and class II MHC molecules. Biopolymers 43:281–302

    Article  CAS  PubMed  Google Scholar 

  • Bhasin M, Raghava GPS (2003) Prediction of promiscuous and high-affinity mutated MHC binders. Hybrid Hybridomics 22:229–234

    Article  CAS  PubMed  Google Scholar 

  • Bhasin M, Raghava GPS (2004a) Prediction of CTL epitopes using QM, SVM and ANN techniques. Vaccine 22:3195–3201

    Article  CAS  PubMed  Google Scholar 

  • Bhasin M, Raghava GPS (2004b) SVM based method for predicting HLA-DRB1 binding peptides in an antigen sequence. Bioinformatics 20:421–423

    Article  CAS  PubMed  Google Scholar 

  • Bhasin M, Raghava GPS (2006) A hybrid approach for predicting promiscuous MHC class I restricted T cell epitopes. J Biosci 32:31–42

    Article  Google Scholar 

  • Bjorkman PJ, Saper MA, Samraoui B et al (1987a) Structure of the human class I histocompatibility antigen, HLA-A2. Nature 329:506–512

    Article  CAS  PubMed  Google Scholar 

  • Bjorkman PJ, Saper MA, Samraoui B et al (1987b) The foreign antigen-binding site and T cell recognition regions of class I histocompatibility antigens. Nature 329:512–518

    Article  CAS  PubMed  Google Scholar 

  • Bodmer JG, Marsh SGE, Albert ED et al (1999) Nomenclature for factors of the HLA system. Tissue Antigens 53:407–446

    Article  CAS  PubMed  Google Scholar 

  • von Boehmer H (1992) Thymic selection: a matter of life and death. Immunol Today 13:454–458

    Article  Google Scholar 

  • Bork P, Holm L, Sander C (1994) The immunoglobulin fold. Structural classification, sequence patterns and common core. J Mol Biol 242:309–320

    PubMed  CAS  Google Scholar 

  • Brown JH, Jardetzky TS, Gorga JC et al (1993) Three-dimensional structure of the human class II histocompatibility antigen HLA-DR1. Nature 364:33–39

    Article  CAS  PubMed  Google Scholar 

  • Brusic V, Rudy G, Harrison LC (1998) MHCPEP, a database of MHC-binding peptides: update 1997. Nucleic Acids Res 26:368–371

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Buus S (1999) Description and prediction of peptide-MHC binding: the ‘human MHC project’. Curr Opin Immunol 11:209–213

    Article  CAS  PubMed  Google Scholar 

  • Chelvanayagam G (1996) A roadmap for HLA-A, HLA-B, and HLA-C peptide binding specificities. Immunogenetics 45:15–26

    Article  CAS  PubMed  Google Scholar 

  • Colbert RA, Rowland-Jones SL, McMichael AJ et al (1994) Differences in peptide presentation between B27 subtypes: the importance of the P1 side chain in maintaining high affinity peptide binding to B*2703. Immunity 1:121–130

    Article  CAS  PubMed  Google Scholar 

  • Collins EJ, Garboczi DN, Karpusas MN et al (1995) The three-dimensional structure of a class I major histocompatibility complex molecule missing the alpha 3 domain of the heavy chain. Proc Natl Acad Sci U S A 92:1218–1221

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cook JR, Myers NB, Hansen TH (1996) The mechanisms of peptide exchange and beta 2-microglobulin exchange on cell surface Ld and Kb molecules are noncooperative. J Immunol 157:2256–2261

    PubMed  CAS  Google Scholar 

  • Corradin G, Demotz S (1997) Peptide-MHC complexes assembled following multiple pathways: an opportunity for the design of vaccines and therapeutic molecules. Hum Immunol 54:137–147

    Article  CAS  PubMed  Google Scholar 

  • Cresswell P (1994) Assembly, transport, and function of MHC class II molecules. Annu Rev Immunol 12:259–293

    Article  CAS  PubMed  Google Scholar 

  • Dawkins R, Leelayuwat C, Gaudieri S et al (1999) Genomics of the major histocompatibility complex: haplotypes, duplication, retroviruses and disease. Immunol Rev 167:275–304

    Article  CAS  PubMed  Google Scholar 

  • Del Guercio MF, Sidney J, Hermanson G et al (1995) Binding of a peptide antigen to multiple HLA alleles allows definition of an A2-like supertype. J Immunol 154:685–693

    PubMed  Google Scholar 

  • Den Haan JM, Meadows LM, Wang W et al (1998) The minor histocompatibility antigen HA-1: a diallelic gene with a single amino acid polymorphism. Science 279:1054–1057

    Article  Google Scholar 

  • Dönnes P, Elofsson A (2002) Prediction of MHC class I binding peptides using SVMHC. BMC Bioinformatics 3:25

    Article  PubMed  PubMed Central  Google Scholar 

  • Doytchinova IA, Guan P, Flower DR (2004) Identifying human MHC supertypes using bioinformatics methods. J Immunol 172:4314–4323

    Article  CAS  PubMed  Google Scholar 

  • Eckels DD (2000) MHC: function and implication on vaccine development. Vox Sang 78(Suppl 2):265–267

    PubMed  CAS  Google Scholar 

  • Falk K, Rotzschke O, Rammensee HG (1990) Cellular peptide composition governed by major histocompatibility complex class I molecules. Nature 348:248–251

    Article  CAS  PubMed  Google Scholar 

  • Guo HC, Jardetzky TS, Garrett TP et al (1992) Different length peptides bind to HLA-Aw68 similarly at their ends but bulge out in the middle. Nature 360:364–366

    Article  CAS  PubMed  Google Scholar 

  • Hakenberg J, Nussbaum A, Schild H et al (2003) MAPPP—MHC-I antigenic peptide processing prediction. Appl Bioinforma 2:155–158

    CAS  Google Scholar 

  • Hattotuwagama CK, Guan P, Doytchinova IA et al (2004) Quantitative online prediction of peptide binding to the major histocompatibility complex. J Mol Graph Model 22:195–207

    Article  CAS  PubMed  Google Scholar 

  • Honeyman MC, Brusic V, Stone NL et al (1998) Neural network-based prediction of candidate T-cell epitopes. Nat Biotechnol 16:966–969

    Article  CAS  PubMed  Google Scholar 

  • Jackson MR, Peterson PA (1993) Assembly and intracellular transport of MHC class I molecules. Annu Rev Cell Biol 9:207–235

    Article  CAS  PubMed  Google Scholar 

  • Jardetzky TS, Lane WS, Robinson RA et al (1991) Identification of self peptides bound to purified HLA-B27. Nature 353:326–329

    Article  CAS  PubMed  Google Scholar 

  • Jardetzky TS, Brown JH, Gorga JC et al (1994) Three-dimensional structure of a human class II histocompatibility molecule complexed with superantigen. Nature 368:711–718

    Article  CAS  PubMed  Google Scholar 

  • Jung C, Kalbus M, Fleckenstein B, Melms A et al (1998) New ligands for HLA DRB1*0301 by random selection of favorable amino acids ranked by competition studies with undecapeptide amide sublibraries. J Immunol Methods 219:139–149

    Article  CAS  PubMed  Google Scholar 

  • Kangueane P, Sakharkar MK (2007a) Grouping of class I HLA alleles using electrostatic distribution maps of the peptide binding grooves. Methods Mol Biol 409:175–181

    Article  CAS  PubMed  Google Scholar 

  • Kangueane P, Sakharkar MK (2007b) Structural basis for HLA-A2 supertypes. Methods Mol Biol 409:155–162

    Article  CAS  PubMed  Google Scholar 

  • Kangueane P, Sakharkar MK, Kolatkar PR et al (2001) Towards the MHC-peptide combinatorics. Hum Immunol 62:539–556

    Article  CAS  PubMed  Google Scholar 

  • Kangueane P, Sakharkar MK, Rajaseger G et al (2005) A framework to sub-type HLA supertypes. Front Biosci 10:879–886

    Article  CAS  PubMed  Google Scholar 

  • Klein J (1986) Natural history of the major histocompatibility complex. Wiley, New York

    Google Scholar 

  • Lee C, McConnell HM (1995) A general model of invariant chain association with class II major histocompatibility complex proteins. Proc Natl Acad Sci U S A 92:8269–8273

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lehmann-Grube F, Dralle H, Utermohlen O et al (1994) MHC class I molecule-restricted presentation of viral antigen in beta 2-microglobulin-deficient mice. J Immunol 153:595–603

    PubMed  CAS  Google Scholar 

  • Lund O, Nielsen M, Kesmir C et al (2004) Definition of supertypes for HLA molecules using clustering of specificity matrices. Immunogenetics 55:797–810

    Article  CAS  PubMed  Google Scholar 

  • Madden DR, Gorga JC, Strominger JL, Wiley DC (1992) The three-dimensional structure of HLA-B27 at 2.1 A resolution suggests a general mechanism for tight peptide binding to MHC. Cell 70(6):1035–1048

    Article  CAS  PubMed  Google Scholar 

  • Madden DR, Gorga JC, Strominger JL et al (1991) The structure of HLA-B27 reveals nonamer self-peptides bound in an extended conformation. Nature 353:321–325

    Article  CAS  PubMed  Google Scholar 

  • Madden DR, Garboczi DN, Wiley DC (1993) The antigenic identity of peptide-MHC complexes: a comparison of the conformations of five viral peptides presented by HLA-A2. Cell 75:693–708

    Article  CAS  PubMed  Google Scholar 

  • Mamitsuka H (1998) Predicting peptides that bind to MHC molecules using supervised learning of hidden Markov models. Proteins 33:460–474

    Article  CAS  PubMed  Google Scholar 

  • Mazza G, Housset D, Piras C et al (1998) Glimpses at the recognition of peptide/MHC complexes by T-cell antigen receptors. Immunol Rev 163:187–196

    Article  CAS  PubMed  Google Scholar 

  • McDevitt HO (2000) Discovering the role of the major histocompatibility complex in the immune response. Annu Rev Immunol 18:1–17

    Article  CAS  PubMed  Google Scholar 

  • Milik M, Sauer D, Brunmark AP et al (1998) Application of an artificial neural network to predict specific class I MHC binding peptide sequences. Nat Biotechnol 16:753–756

    Article  CAS  PubMed  Google Scholar 

  • Murthy VL, Stern LJ (1997) The class II MHC protein HLA-DR1 in complex with an endogenous peptide: implications for the structural basis of the specificity of peptide binding. Structure 5:1385–1396

    Article  CAS  PubMed  Google Scholar 

  • Neefjes JJ, Momburg F (1993) Cell biology of antigen presentation. Curr Opin Immunol 5:27–34

    Article  CAS  PubMed  Google Scholar 

  • Nielsen M, Lundegaard C, Worning P et al (2004) Improved prediction of MHC class I and class II epitopes using a novel Gibbs sampling approach. Bioinformatics 20:1388–1397

    Article  CAS  PubMed  Google Scholar 

  • Ortmann B, Androlewicz MJ, Cresswell P (1994) MHC class I/beta 2-microglobulin complexes associate with TAP transporters before peptide binding. Nature 368:864–867

    Article  CAS  PubMed  Google Scholar 

  • Parker KC, Bednarek MA, Coligan JE (1994) Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains. J Immunol 152:163–175

    PubMed  CAS  Google Scholar 

  • Peters PJ, Raposo G, Neefjes JJ et al (1995) Major histocompatibility complex class II compartments in human B lymphoblastoid cells are distinct from early endosomes. J Exp Med 182:325–334

    Article  CAS  PubMed  Google Scholar 

  • Peters B, Tong W, Sidney J et al (2003) Examining the independent binding assumption for binding of peptide epitopes to MHC-I molecules. Bioinformatics 19:1765–1772

    Article  CAS  PubMed  Google Scholar 

  • Pogue RR, Eron J, Frelinger JA et al (1995) Amino-terminal alteration of the HLA-A*0201-restricted human immunodeficiency virus pol peptide increases complex stability and in vitro immunogenicity. Proc Natl Acad Sci U S A 92:8166–8170

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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 

  • Rammensee HG, Friede T, Stevanoviic S (1995) MHC ligands and peptide motifs: first listing. Immunogenetics 41:178–228

    Article  CAS  PubMed  Google Scholar 

  • Rammensee H, Bachmann J, Emmerich NN et al (1999) SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 50:213–219

    Article  CAS  PubMed  Google Scholar 

  • Reche PA, Reinherz EL (2003) Sequence variability analysis of human class-I and class-II MHC molecules: functional and structural correlates of amino acid polymorphisms. J Mol Biol 331:623–641

    Article  CAS  PubMed  Google Scholar 

  • Robinson J, Waller MJ, Parham P et al (2003) IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex. Nucleic Acids Res 31:311–314

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rock KL, Gramm C, Rothstein L et al (1994) Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules. Cell 78:761–771

    Article  CAS  PubMed  Google Scholar 

  • Rudensky AY, Maric M, Eastman S et al (1994) Intracellular assembly and transport of endogenous peptide-MHC class II complexes. Immunity 1:585–594

    Article  CAS  PubMed  Google Scholar 

  • Ruppert J, Sidney J, Celis E et al (1993) Prominent role of secondary anchor residues in peptide binding to HLA-A2.1 molecules. Cell 74:929–937

    Article  CAS  PubMed  Google Scholar 

  • Sathiamurthy M, Hickman HD, Cavett JW et al (2003) Population of the HLA ligand database. Tissue Antigens 61:12–19

    Article  CAS  PubMed  Google Scholar 

  • Schafer JR, Jesdale BM, George JA et al (1998) Prediction of well-conserved HIV-1 ligands using a matrix-based algorithm, EpiMatrix. Vaccine 16:1880–1884

    Article  CAS  PubMed  Google Scholar 

  • Schueler-Furman O, Elber R, Margalit H (1998) Knowledge-based structure prediction of MHC class I bound peptides: a study of 23 complexes. Fold Des 3:549–564

    Article  CAS  PubMed  Google Scholar 

  • Sette A, Sidney J (1998) HLA supertypes and supermotifs—a functional perspective on HLA polymorphism. Curr Opin Immunol 10:478–482

    Article  CAS  PubMed  Google Scholar 

  • Sette A, Vitiello A, Reherman B et al (1994) The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J Immunol 153:5586–5592

    PubMed  CAS  Google Scholar 

  • Sette A, Newman M, Livingston B et al (2002) Optimizing vaccine design for cellular processing, MHC binding and TCR recognition. Tissue Antigens 59:443–451

    Article  CAS  PubMed  Google Scholar 

  • Sidney J, Southwood S, Pasquetto V et al (2003) Simultaneous prediction of binding capacity for multiple molecules of the HLA B44 supertype. J Immunol 171:5964–5974

    Article  CAS  PubMed  Google Scholar 

  • Singh H, Raghava GPS (2001) ProPred: prediction of HLA-DR binding sites. Bioinformatics 17:1236–1237

    Article  CAS  PubMed  Google Scholar 

  • Singh H, Raghava GPS (2003) ProPred1: prediction of promiscuous MHC class-I binding sites. Bioinformatics 19:1009–10014

    Article  CAS  PubMed  Google Scholar 

  • 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 368:215–221

    Article  CAS  PubMed  Google Scholar 

  • Suh WK, Cohen-Doyle MF, Fruh K et al (1994) Interaction of MHC class I molecules with the transporter associated with antigen processing. Science 264:1322–1326

    Article  CAS  PubMed  Google Scholar 

  • The MHC Sequencing Consortium (1999) The complete sequence and gene map of a human major histocompatibility complex. Nature 401:921–923

    Article  Google Scholar 

  • Tiwari JL, Terasaki PI (1985) HLA and disease associations. Springer, Berlin

    Book  Google Scholar 

  • Townsend A, Elliott T, Cerundolo V et al (1990) Assembly of MHC class I molecules analyzed in vitro. Cell 62:285–295

    Article  CAS  PubMed  Google Scholar 

  • Turner S, Ellexson ME, Hickman HD et al (1998) Sequence-based typing provides a new look at HLA-C diversity. J Immunol 161:1406–1413

    PubMed  CAS  Google Scholar 

  • Uebel S, Tampe R (1999) Specificity of the proteasome and the TAP transporter. Curr Opin Immunol 11:203–208

    Article  CAS  PubMed  Google Scholar 

  • Venkatarajan MS, Braun W (2001) New quantitative descriptor of amino acids based on multi-dimensional scaling of a large number of physical-chemical properties. J Mol Model 7:445–456

    Article  CAS  Google Scholar 

  • Wilke M, Pool J, den Haan JMM et al (1998) Genomic identification of the minor histocompatibility antigen HA-1 locus by allele-specific PCR. Tissue Antigens 52:312–317

    Article  CAS  PubMed  Google Scholar 

  • Yewdell JW, Reits E, Neefjes J (2003) Making sense of mass destruction—quantitating MHC class I antigen presentation. Nat Rev Immunol 3:952–961

    Article  CAS  PubMed  Google Scholar 

  • Zhang C, Anderson A, DeLisi C (1998) Structural principles that govern the peptide binding motifs of class I MHC molecules. J Mol Biol 281:929–947

    Article  CAS  PubMed  Google Scholar 

  • Zhao B, Mathura VS, Rajaseger G et al (2003a) A novel MHCp binding prediction model. Hum Immunol 64:1123–1143

    Article  CAS  PubMed  Google Scholar 

  • Zhao B, Png AEH, Ren EC et al (2003b) Compression of functional space in HLA-A sequence diversity. Hum Immunol 64:718–728

    Article  CAS  PubMed  Google Scholar 

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  1. Pondicherry, India

    Pandjassarame Kangueane

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Kangueane, P. (2018). MHC Informatics to Peptide Vaccine Design. In: Bioinformation Discovery. Springer, Cham. https://doi.org/10.1007/978-3-319-95327-4_7

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