The utility and limitations of current web-available algorithms to predict peptides recognized by CD4 T cells in response to pathogen infection

Journal of Immunology

Volumn 188, Issue 9, 2012, Pages 4235-4248

  Chaves, Francisco A ^a   Lee, Alvin H ^a   Nayak, Jennifer L ^a   Richards, Katherine A ^a   Sant, Andrea J ^a  

^a UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOKINE; EPITOPE; MAJOR HISTOCOMPATIBILITY ANTIGEN CLASS 2; PEPTIDE;

ACCURACY; ALGORITHM; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIGEN RECOGNITION; ARTICLE; CD4+ T LYMPHOCYTE; COMPLEX FORMATION; COMPUTER PREDICTION; CONTROLLED STUDY; FALSE NEGATIVE RESULT; FALSE POSITIVE RESULT; IMMUNE RESPONSE; INFLUENZA; INTERNET; MOUSE; NONHUMAN; PRIORITY JOURNAL; RECEIVER OPERATING CHARACTERISTIC;

ALGORITHMS; ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; COMPUTER SIMULATION; EPITOPES; HISTOCOMPATIBILITY ANTIGENS CLASS II; HUMANS; INFECTION; INTERNET; MICE; MICE, TRANSGENIC; PEPTIDES; SEQUENCE ANALYSIS, DNA;

EID: 84860320829     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.1103640     Document Type: Article

References (111)

1. De Groot, A. S., and R. Rappuoli. 2004. Genome-derived vaccines. Expert Rev. Vaccines 3: 59-76. (Pubitemid 38202173)
2. Herrera-Najera, C., R. Piña-Aguilar, F. Xacur-Garcia, M. J. Ramirez-Sierra, and E. Dumonteil. 2009. Mining the Leishmania genome for novel antigens and vaccine candidates. Proteomics 9: 1293-1301.
3. Sette, A., and R. Rappuoli. 2010. Reverse vaccinology: developing vaccines in the era of genomics. Immunity 33: 530-541.
4. Chaudhuri, R., S. Ahmed, F. A. Ansari, H. V. Singh, and S. Ramachandran. 2008. MalVac: database of malarial vaccine candidates. Malar. J. 7: 184.
5. Dudek, N. L., P. Perlmutter, M. I. Aguilar, N. P. Croft, and A. W. Purcell. 2010. Epitope discovery and their use in peptide based vaccines. Curr. Pharm. Des. 16: 3149-3157.
6. Shimonkevitz, R., S. Colon, J. W. Kappler, P. Marrack, and H. M. Grey. 1984. Antigen recognition by H-2-restricted T cells. II. A tryptic ovalbumin peptide that substitutes for processed antigen. J. Immunol. 133: 2067-2074. (Pubitemid 14035311)
7. Allen, P. M., D. J. Strydom, and E. R. Unanue. 1984. Processing of lysozyme by macrophages: identification of the determinant recognized by two T-cell hybridomas. Proc. Natl. Acad. Sci. USA 81: 2489-2493.
8. Villarreal-Ramos, B., J. Sanchez-Garcia, N. Stoker, E. Timms, D. Chomer, K. Raff, and N. A. Mitchison. 1991. Screening gene expression libraries for epitopes recognized in Mycobacterium leprae by mouse T cells. Eur. J. Immunol. 21: 2621-2624.
9. Kurokohchi, K., T. Akatsuka, C. D. Pendleton, A. Takamizawa, M. Nishioka, M. Battegay, S. M. Feinstone, and J. A. Berzofsky. 1996. Use of recombinant protein to identify a motif-negative human cytotoxic T-cell epitope presented by HLA-A2 in the hepatitis C virus NS3 region. J. Virol. 70: 232-240. (Pubitemid 126508790)
10. Turner, M. J., C. S. Abdul-Alim, R. A. Willis, T. L. Fisher, E. M. Lord, and J. G. Frelinger. 2001. T-cell antigen discovery (T-CAD) assay: a novel technique for identifying T cell epitopes. J. Immunol. Methods 256: 107-119. (Pubitemid 32769921)
11. Valentino, M. D., Z. J. Maben, L. L. Hensley, M. D. Woolard, T. H. Kawula, J. A. Frelinger, and J. G. Frelinger. 2011. Identification of T-cell epitopes in Francisella tularensis using an ordered protein array of serological targets. Immunology 132: 348-360.
12. Reinhold, B., D. B. Keskin, and E. L. Reinherz. 2010. Molecular detection of targeted major histocompatibility complex I-bound peptides using a probabilistic measure and nanospray MS(3) on a hybrid quadrupole-linear ion trap. Anal. Chem. 82: 9090-9099.
13. Purcell, A. W., and J. J. Gorman. 2001. The use of post-source decay in matrix-assisted laser desorption/ionisation mass spectrometry to delineate T cell determinants. J. Immunol. Methods 249: 17-31. (Pubitemid 32171955)
14. Karunakaran, K. P., J. Rey-Ladino, N. Stoynov, K. Berg, C. Shen, X. Jiang, B. R. Gabel, H. Yu, L. J. Foster, and R. C. Brunham. 2008. Immunoproteomic discovery of novel T cell antigens from the obligate intracellular pathogen Chlamydia. J. Immunol. 180: 2459-2465.
15. Tan, C. T., N. P. Croft, N. L. Dudek, N. A. Williamson, and A. W. Purcell. 2011. Direct quantitation of MHC-bound peptide epitopes by selected reaction monitoring. Proteomics 11: 2336-2340.
16. Strug, I., J. M. Calvo-Calle, K. M. Green, J. Cruz, F. A. Ennis, J. E. Evans, and L. J. Stern. 2008. Vaccinia peptides eluted from HLA-DR1 isolated from virus-infected cells are recognized by CD4+ T cells from a vaccinated donor. J. Proteome Res. 7: 2703-2711.
17. Hiemstra, H. S., J. W. Drijfhout, and F. Koning. 2000. Synthetic peptide libraries for T-cell epitope identification. Methods Mol. Med. 41: 89-96.
18. Geginat, G., S. Schenk, M. Skoberne, W. Goebel, and H. Hof. 2001. A novel approach of direct ex vivo epitope mapping identifies dominant and subdominant CD4 and CD8 T cell epitopes from Listeria monocytogenes. J. Immunol. 166: 1877-1884. (Pubitemid 32114674)
19. Tobery, T. W., and M. J. Caulfield. 2004. Identification of T-cell epitopes using ELISpot and peptide pool arrays. Methods Mol. Med. 94: 121-132.
20. Maciel, M., Jr., S. N. Kellathur, P. Chikhlikar, R. Dhalia, J. Sidney, A. Sette, T. J. August, and E. T. Marques, Jr. 2008. Comprehensive analysis of T cell epitope discovery strategies using 17DD yellow fever virus structural proteins and BALB/c (H2d) mice model. Virology 378: 105-117.
21. Richards, K. A., F. A. Chaves, and A. J. Sant. 2009. Infection of HLA-DR1 transgenic mice with a human isolate of influenza a virus (H1N1) primes a diverse CD4 T-cell repertoire that includes CD4 T cells with heterosubtypic cross-reactivity to avian (H5N1) influenza virus. J. Virol. 83: 6566-6577.
22. Nayak, J. L., K. A. Richards, F. A. Chaves, and A. J. Sant. 2010. Analyses of the specificity of CD4 T cells during the primary immune response to influenza virus reveals dramatic MHC-linked asymmetries in reactivity to individual viral proteins. Viral Immunol. 23: 169-180.
23. Zhang, H., P. Wang, N. Papangelopoulos, Y. Xu, A. Sette, P. E. Bourne, O. Lund, J. Ponomarenko, M. Nielsen, and B. Peters. 2010. Limitations of Ab initio predictions of peptide binding to MHC class II molecules. PLoS ONE 5: e9272.
24. Wang, P., J. Sidney, Y. Kim, A. Sette, O. Lund, M. Nielsen, and B. Peters. 2010. Peptide binding predictions for HLA DR, DP and DQ molecules. BMC Bioinformatics 11: 568.
25. Lin, H. H., G. L. Zhang, S. Tongchusak, E. L. Reinherz, and V. Brusic. 2008. Evaluation of MHC-II peptide binding prediction servers: applications for vaccine research. BMC Bioinformatics 9(Suppl 12): S22.
26. Lin, H. H., S. Ray, S. Tongchusak, E. L. Reinherz, and V. Brusic. 2008. Evaluation of MHC class I peptide binding prediction servers: applications for vaccine research. BMC Immunol. 9: 8.
27. Peters, B., H. H. Bui, S. Frankild, M. Nielson, C. Lundegaard, E. Kostem, D. Basch, K. Lamberth, M. Harndahl, W. Fleri, et al. 2006. A community resource benchmarking predictions of peptide binding to MHC-I molecules. PLOS Comput. Biol. 2: e65.
28. Nielsen, M., O. Lund, S. Buus, and C. Lundegaard. 2010. MHC class II epitope predictive algorithms. Immunology 130: 319-328.
29. Nielsen, M., C. Lundegaard, and O. Lund. 2007. Prediction of MHC class II binding affinity using SMM-align, a novel stabilization matrix alignment method. BMC Bioinformatics 8: 238.
30. Bui, H. H., J. Sidney, B. Peters, M. Sathiamurthy, A. Sinichi, K. A. Purton, B. R. Mothé, F. V. Chisari, D. I. Watkins, and A. Sette. 2005. Automated generation and evaluation of specific MHC binding predictive tools: ARB matrix applications. Immunogenetics 57: 304-314. (Pubitemid 40905049)
31. Zhang, G. L., A. M. Khan, K. N. Srinivasan, J. T. August, and V. Brusic. 2005. Neural models for predicting viral vaccine targets. J. Bioinform. Comput. Biol. 3: 1207-1225. (Pubitemid 41683437)
32. Nielsen, M., and O. Lund. 2009. NN-align. An artificial neural network-based alignment algorithm for MHC class II peptide binding prediction. BMC Bioinformatics 10: 296.
33. Zhang, W., J. Liu, and Y. Niu. 2010. Quantitative prediction of MHC-II binding affinity using particle swarm optimization. Artif. Intell. Med. 50: 127-132.
34. Wang, P., J. Sidney, C. Dow, B. Mothé, A. Sette, and B. Peters. 2008. A systematic assessment of MHC class II peptide binding predictions and evaluation of a consensus approach. PLOS Comput. Biol. 4: e1000048.
35. Falk, K., O. Rötzschke, S. Stevanović, G. Jung, and H. G. Rammensee. 1991. Allele-specific motifs revealed by sequencing of self-peptides eluted from MHC molecules. Nature 351: 290-296. (Pubitemid 21896578)
36. Deres, K., T. N. Schumacher, K. H. Wiesmüller, S. Stevanović, G. Greiner, G. Jung, and H. L. Ploegh. 1992. Preferred size of peptides that bind to H-2 Kb is sequence dependent. Eur. J. Immunol. 22: 1603-1608.
37. Matsumura, M., D. H. Fremont, P. A. Peterson, and I. A. Wilson. 1992. Emerging principles for the recognition of peptide antigens by MHC class I molecules. Science 257: 927-934.
38. Chicz, R. M., R. G. Urban, W. S. Lane, J. C. Gorga, L. J. Stern, D. A. Vignali, and J. L. Strominger. 1992. Predominant naturally processed peptides bound to HLA-DR1 are derived from MHC-related molecules and are heterogeneous in size. Nature 358: 764-768.
39. Hunt, D. F., H. Michel, T. A. Dickinson, J. Shabanowitz, A. L. Cox, K. Sakaguchi, E. Appella, H. M. Grey, and A. Sette. 1992. Peptides presented to the immune system by the murine class II major histocompatibility complex molecule I-Ad. Science 256: 1817-1820.
40. Lippolis, J. D., F. M. White, J. A. Marto, C. J. Luckey, T. N. Bullock, J. Shabanowitz, D. F. Hunt, and V. H. Engelhard. 2002. Analysis of MHC class II antigen processing by quantitation of peptides that constitute nested sets. J. Immunol. 169: 5089-5097. (Pubitemid 35217178)
41. Srinivasan, M., S. Z. Domanico, P. T. Kaumaya, and S. K. Pierce. 1993. Peptides of 23 residues or greater are required to stimulate a high affinity class II-restricted T cell response. Eur. J. Immunol. 23: 1011-1016. (Pubitemid 23120158)
42. Landais, E., P. A. Romagnoli, A. L. Corper, J. Shires, J. D. Altman, I. A. Wilson, K. C. Garcia, and L. Teyton. 2009. New design of MHC class II tetramers to accommodate fundamental principles of antigen presentation. J. Immunol. 183: 7949-7957.
43. Bankovich, A. J., A. T. Girvin, A. K. Moesta, and K. C. Garcia. 2004. Peptide register shifting within the MHC groove: theory becomes reality. Mol. Immunol. 40: 1033-1039. (Pubitemid 38221183)
44. Robertson, J. M., P. E. Jensen, and B. D. Evavold. 2000. DO11.10 and OT-II T cells recognize a C-terminal ovalbumin 323-339 epitope. J. Immunol. 164: 4706-4712. (Pubitemid 30238071)
45. McFarland, B. J., A. J. Sant, T. P. Lybrand, and C. Beeson. 1999. Ovalbumin (323-339) peptide binds to the major histocompatibility complex class II I-A(d) protein using two functionally distinct registers. Biochemistry 38: 16663-16670.
46. Peters, B., J. Sidney, P. Bourne, H. H. Bui, S. Buus, G. Doh, W. Fleri, M. Kronenberg, R. Kubo, O. Lund, et al. 2005. The immune epitope database and analysis resource: from vision to blueprint. PLoS Biol. 3: e91.
47. Peters, B., J. Sidney, P. Bourne, H. H. Bui, S. Buus, G. Doh, W. Fleri, M. Kronenberg, R. Kubo, O. Lund, et al. 2005. The design and implementation of the immune epitope database and analysis resource. Immunogenetics 57: 326-336. (Pubitemid 40905051)
48. Zhang, G. L., H. H. Lin, D. B. Keskin, E. L. Reinherz, and V. Brusic. 2011. Dana-Farber repository for machine learning in immunology. J. Immunol. Methods 374: 18-25.
49. Nielsen, M., S. Justesen, O. Lund, C. Lundegaard, and S. Buus. 2010. NetMHCIIpan-2.0 - improved pan-specific HLA-DR predictions using a novel concurrent alignment and weight optimization training procedure. Immunome Res. 6: 9.
50. Dimitrov, I., P. Garnev, D. R. Flower, and I. Doytchinova. 2010. MHC class II binding prediction - a little help from a friend. J. Biomed. Biotechnol. 2010: 705821.
51. Hu, X., W. Zhou, K. Udaka, H. Mamitsuka, and S. Zhu. 2010. MetaMHC: a meta approach to predict peptides binding to MHC molecules. Nucleic Acids Res. 38(Web Server issue): W474-9.
52. Mustafa, A. S., F. A. Shaban, R. Al-Attiyah, A. T. Abal, A. M. El-Shamy, P. Andersen, and F. Oftung. 2003. Human Th1 cell lines recognize the Mycobacterium tuberculosis ESAT-6 antigen and its peptides in association with frequently expressed HLA class II molecules. Scand. J. Immunol. 57: 125-134. (Pubitemid 36232879)
53. Zhao, B. P., L. Chen, Y. L. Zhang, J. M. Yang, K. Jia, C. Y. Sui, C. X. Yuan, J. J. Lin, and X. G. Feng. 2011. In silico prediction of binding of promiscuous peptides to multiple MHC class-II molecules identifies the Th1 cell epitopes from secreted and transmembrane proteins of Schistosoma japonicum in BALB/c mice. Microbes Infect. 13: 709-719.
54. Foo, D. G., P. A. Macary, S. Alonso, and C. L. Poh. 2008. Identification of human CD4 T-cell epitopes on the VP1 capsid protein of enterovirus 71. Viral Immunol. 21: 215-224. (Pubitemid 351873363)
55. Fonseca, C. T., E. Cunha-Neto, A. C. Goldberg, J. Kalil, A. R. de Jesus, E. M. Carvalho, R. Correa-Oliveira, J. Hammer, J. Sidney, A. Sette, and S. C. Oliveira. 2005. Identification of paramyosin T cell epitopes associated with human resistance to Schistosoma mansoni reinfection. Clin. Exp. Immunol. 142: 539-547. (Pubitemid 41719851)
56. Richards, K. A., F. A. Chaves, and A. J. Sant. 2011. The memory phase of the CD4 T-cell response to influenza virus infection maintains its diverse antigen specificity. Immunology 133: 246-256.
57. Lazarski, C. A., F. A. Chaves, S. A. Jenks, S. Wu, K. A. Richards, J. M. Weaver, and A. J. Sant. 2005. The kinetic stability of MHC class II: peptide complexes is a key parameter that dictates immunodominance. Immunity 23: 29-40. (Pubitemid 41019655)
58. Chaves, F. A., and A. J. Sant. 2007. Measurement of peptide dissociation from MHC class II molecules. Curr. Protoc. Immunol. Chapter 18: Unit 18.14.
59. Chaves, F. A., K. A. Richards, A. Torelli, J. Wedekind, and A. J. Sant. 2006. Peptide-binding motifs for the I-Ad MHC class II molecule: alternate pH-dependent binding behavior. Biochemistry 45: 6426-6433. (Pubitemid 43787808)
60. Chaves, F. A., P. Hou, S. Wu, and A. J. Sant. 2005. Replacement of the membrane proximal region of I-A(d) MHC class II molecule with I-E-derived sequences promotes production of an active and stable soluble heterodimer without altering peptide-binding specificity. J. Immunol. Methods 300: 74-92. (Pubitemid 40805589)
61. Nelson, P. A., M. Khodadoust, T. Prodhomme, C. Spencer, J. C. Patarroyo, M. Varrin-Doyer, J. D. Ho, R. M. Stroud, and S. S. Zamvil. 2010. Immunodominant T cell determinants of aquaporin-4, the autoantigen associated with neuromyelitis optica. PLoS ONE 5: e15050.
62. Akhoon, B. A., P. S. Slathia, P. Sharma, S. K. Gupta, and V. Verma. 2011. In silico identification of novel protective VSG antigens expressed by Trypanosoma brucei and an effort for designing a highly immunogenic DNA vaccine using IL-12 as adjuvant. Microb. Pathog. 51: 77-87.
63. Bordner, A. J., and H. D. Mittelmann. 2010. Prediction of the binding affinities of peptides to class II MHC using a regularized thermodynamic model. BMC Bioinformatics 11: 41.
64. Nielsen, M., C. Lundegaard, T. Blicher, B. Peters, A. Sette, S. Justesen, S. Buus, and O. Lund. 2008. Quantitative predictions of peptide binding to any HLA-DR molecule of known sequence: NetMHCIIpan. PLOS Comput. Biol. 4: e1000107.
65. Richards, K. A., F. A. Chaves, F. R. Krafcik, D. J. Topham, C. A. Lazarski, and A. J. Sant. 2007. Direct ex vivo analyses of HLA-DR1 transgenic mice reveal an exceptionally broad pattern of immunodominance in the primary HLA-DR1-restricted CD4 T-cell response to influenza virus hemagglutinin. J. Virol. 81: 7608-7619. (Pubitemid 47047846)
66. Tobery, T. W., S. Wang, X. M. Wang, M. P. Neeper, K. U. Jansen, W. L. McClements, and M. J. Caulfield. 2001. A simple and efficient method for the monitoring of antigen-specific T cell responses using peptide pool arrays in a modified ELISpot assay. J. Immunol. Methods 254: 59-66. (Pubitemid 32530748)
67. Sturniolo, T., E. Bono, J. Ding, L. Raddrizzani, O. Tuereci, U. Sahin, M. Braxenthaler, F. Gallazzi, M. P. Protti, F. Sinigaglia, and J. Hammer. 1999. Generation of tissue-specific and promiscuous HLA ligand databases using DNA microarrays and virtual HLA class II matrices. Nat. Biotechnol. 17: 555-561. (Pubitemid 29262918)
68. Cantor, J. R., T. H. Yoo, A. Dixit, B. L. Iverson, T. G. Forsthuber, and G. Georgiou. 2011. Therapeutic enzyme deimmunization by combinatorial T-cell epitope removal using neutral drift. Proc. Natl. Acad. Sci. USA 108: 1272-1277.
69. Yauch, L. E., T. R. Prestwood, M. M. May, M. M. Morar, R. M. Zellweger, B. Peters, A. Sette, and S. Shresta. 2010. CD4+ T cells are not required for the induction of dengue virus-specific CD8+ T cell or antibody responses but contribute to protection after vaccination. J. Immunol. 185: 5405-5416.
70. Chen, C., C. Dow, P. Wang, J. Sidney, A. Read, A. Harmsen, J. E. Samuel, and B. Peters. 2011. Identification of CD4+ T cell epitopes in C. burnetii antigens targeted by antibody responses. PLoS ONE 6: e17712.
71. Arens, R., P. Wang, J. Sidney, A. Loewendorf, A. Sette, S. P. Schoenberger, B. Peters, and C. A. Benedict. 2008. Cutting edge: murine cytomegalovirus induces a polyfunctional CD4 T cell response. J. Immunol. 180: 6472-6476.
72. Chicz, R. M., R. G. Urban, J. C. Gorga, D. A. Vignali, W. S. Lane, and J. L. Strominger. 1993. Specificity and promiscuity among naturally processed peptides bound to HLA-DR alleles. J. Exp. Med. 178: 27-47. (Pubitemid 23173241)
73. Sant, A. J. 1994. Endogenous antigen presentation by MHC class II molecules. Immunol. Res. 13: 253-267.
74. Loss, G. E., Jr., C. G. Elias, P. E. Fields, R. K. Ribaudo, M. McKisic, and A. J. Sant. 1993. Major histocompatibility complex class II-restricted presentation of an internally synthesized antigen displays cell-type variability and segregates from the exogenous class II and endogenous class I presentation pathways. J. Exp. Med. 178: 73-85. (Pubitemid 23173244)
75. Swets, J. A. 1988. Measuring the accuracy of diagnostic systems. Science 240: 1285-1293.
76. Calvo-Calle, J. M., I. Strug, M. D. Nastke, S. P. Baker, and L. J. Stern. 2007. Human CD4+ T cell epitopes from vaccinia virus induced by vaccination or infection. PLoS Pathog. 3: 1511-1529. (Pubitemid 350085615)
77. Sant, A. J., F. A. Chaves, S. A. Jenks, K. A. Richards, P. Menges, J. M. Weaver, and C. A. Lazarski. 2005. The relationship between immunodominance, DM editing, and the kinetic stability of MHC class II: peptide complexes. Immunol. Rev. 207: 261-278. (Pubitemid 41415023)
78. Sant, A. J., F. A. Chaves, F. R. Krafcik, C. A. Lazarski, P. Menges, K. Richards, and J. M. Weaver. 2007. Immunodominance in CD4 T-cell responses: implications for immune responses to influenza virus and for vaccine design. Expert Rev. Vaccines 6: 357-368. (Pubitemid 46911599)
79. Weaver, J. M., C. A. Lazarski, K. A. Richards, F. A. Chaves, S. A. Jenks, P. R. Menges, and A. J. Sant. 2008. Immunodominance of CD4 T cells to foreign antigens is peptide intrinsic and independent of molecular context: implications for vaccine design. J. Immunol. 181: 3039-3048.
80. Weaver, J. M., F. A. Chaves, and A. J. Sant. 2009. Abortive activation of CD4 T cell responses during competitive priming in vivo. Proc. Natl. Acad. Sci. USA 106: 8647-8652.
81. Kasson, P. M., J. D. Rabinowitz, L. Schmitt, M. M. Davis, and H. M. McConnell. 2000. Kinetics of peptide binding to the class II MHC protein I-Ek. Biochemistry 39: 1048-1058. (Pubitemid 30075333)
82. Lazarski, C. A., F. A. Chaves, and A. J. Sant. 2006. The impact of DM on MHC class II-restricted antigen presentation can be altered by manipulation of MHC-peptide kinetic stability. J. Exp. Med. 203: 1319-1328. (Pubitemid 43736600)
83. Grotenbreg, G. M., N. R. Roan, E. Guillen, R. Meijers, J. H. Wang, G. W. Bell, M. N. Starnbach, and H. L. Ploegh. 2008. Discovery of CD8+ T cell epitopes in Chlamydia trachomatis infection through use of caged class I MHC tetramers. Proc. Natl. Acad. Sci. USA 105: 3831-3836. (Pubitemid 351723485)
84. Roti, M., J. Yang, D. Berger, L. Huston, E. A. James, and W. W. Kwok. 2008. Healthy human subjects have CD4+ T cells directed against H5N1 influenza virus. J. Immunol. 180: 1758-1768.
85. Yang, J., E. A. James, L. Huston, N. A. Danke, A. W. Liu, and W. W. Kwok. 2006. Multiplex mapping of CD4 T cell epitopes using class II tetramers. Clin. Immunol. 120: 21-32. (Pubitemid 43903391)
86. Reijonen, H., and W. W. Kwok. 2003. Use of HLA class II tetramers in tracking antigen-specific T cells and mapping T-cell epitopes. Methods 29: 282-288. (Pubitemid 36513444)
87. Salimi, N., W. Fleri, B. Peters, and A. Sette. 2010. Design and utilization of epitope-based databases and predictive tools. Immunogenetics 62: 185-196.
88. Zhang, Q., P. Wang, Y. Kim, P. Haste-Andersen, J. Beaver, P. E. Bourne, H. H. Bui, S. Buus, S. Frankild, J. Greenbaum, et al. 2008. Immune epitope database analysis resource (IEDB-AR). Nucleic Acids Res. 36(Web Server issue): W513-8.
89. Chung, J. L., J. Sun, J. Sidney, A. Sette, and B. Peters. 2010. IMMUNOCAT - a data management system for epitope mapping studies. J. Biomed. Biotechnol. 2010: 856842.
90. Ge, X., J. A. Gebe, P. L. Bollyky, E. A. James, J. Yang, L. J. Stern, and W. W. Kwok. 2010. Peptide-MHC cellular microarray with innovative data analysis system for simultaneously detecting multiple CD4 T-cell responses. PLoS ONE 5: e11355.
91. Scott, C. A., P. A. Peterson, L. Teyton, and I. A. Wilson. 1998. Crystal structures of two I-Ad-peptide complexes reveal that high affinity can be achieved without large anchor residues. [erratum appears in Immunity 1998;8(4): 531]
92. Immunity 8: 319-329.
93. Sette, A., S. Buus, S. Colon, C. Miles, and H. M. Grey. 1988. I-Ad-binding peptides derived from unrelated protein antigens share a common structural motif. J. Immunol. 141: 45-48.
94. Hulme, E. C., and M. A. Trevethick. 2010. Ligand binding assays at equilibrium: validation and interpretation. Br. J. Pharmacol. 161: 1219-1237.
95. Zettner, A. 1974. Some theoretical aspects of competitive binding assays. Hum. Pathol. 5: 6-8.
96. Zettner, A. 1973. Principles of competitive binding assays (saturation analysis). 1. Equilibrium techniques. Clin. Chem. 19: 699-705.
97. Cheng, Y., and W. H. Prusoff. 1973. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem. Pharmacol. 22: 3099-3108.
98. Beeson, C., and H. M. McConnell. 1994. Kinetic intermediates in the reactions between peptides and proteins of major histocompatibility complex class II. Proc. Natl. Acad. Sci. USA 91: 8842-8845.
99. de Kroon, A. I., and H. M. McConnell. 1994. Kinetics and specificity of peptide-MHC class II complex displacement reactions. J. Immunol. 152: 609-619. (Pubitemid 24072964)
100. Beeson, C., and H. M. McConnell. 1995. Reactions of peptides with class II proteins of the major histocompatibility complex. J. Am. Chem. Soc. 117: 10429-10433.
101. Zarutskie, J. A., R. Busch, Z. Zavala-Ruiz, M. Rushe, E. D. Mellins, and L. J. Stern. 2001. The kinetic basis of peptide exchange catalysis by HLA-DM. Proc. Natl. Acad. Sci. USA 98: 12450-12455. (Pubitemid 33019966)
102. Sadegh-Nasseri, S., and H. M. McConnell. 1989. A kinetic intermediate in the reaction of an antigenic peptide and I-Ek. Nature 337: 274-276. (Pubitemid 19030566)
103. Turner, S. J., K. Kedzierska, H. Komodromou, N. L. La Gruta, M. A. Dunstone, A. I. Webb, R. Webby, H. Walden, W. Xie, J. McCluskey, et al. 2005. Lack of prominent peptide-major histocompatibility complex features limits repertoire diversity in virus-specific CD8+ T cell populations. Nat. Immunol. 6: 382-389. (Pubitemid 41716778)
104. Hogquist, K. A., T. A. Baldwin, and S. C. Jameson. 2005. Central tolerance: learning self-control in the thymus. Nat. Rev. Immunol. 5: 772-782. (Pubitemid 41400851)
105. Chen, J. L., G. Stewart-Jones, G. Bossi, N. M. Lissin, L. Wooldridge, E. M. Choi, G. Held, P. R. Dunbar, R. M. Esnouf, M. Sami, et al. 2005. Structural and kinetic basis for heightened immunogenicity of T cell vaccines. J. Exp. Med. 201: 1243-1255. (Pubitemid 40629068)
106. Stewart-Jones, G. B., A. J. McMichael, J. I. Bell, D. I. Stuart, and E. Y. Jones. 2003. A structural basis for immunodominant human T cell receptor recognition. Nat. Immunol. 4: 657-663. (Pubitemid 36874442)
107. Rudolph, M. G., R. L. Stanfield, and I. A. Wilson. 2006. How TCRs bind MHCs, peptides, and coreceptors. Annu. Rev. Immunol. 24: 419-466.
108. Chu, H. H., J. J. Moon, A. C. Kruse, M. Pepper, and M. K. Jenkins. 2010. Negative selection and peptide chemistry determine the size of naive foreign peptide-MHC class II-specific CD4+ T cell populations. J. Immunol. 185: 4705-4713.
109. Obar, J. J., K. M. Khanna, and L. Lefrançois. 2008. Endogenous naive CD8+ T cell precursor frequency regulates primary and memory responses to infection. Immunity 28: 859-869.
110. Kosmrlj, A., A. K. Jha, E. S. Huseby, M. Kardar, and A. K. Chakraborty. 2008. How the thymus designs antigen-specific and self-tolerant T cell receptor sequences. Proc. Natl. Acad. Sci. USA 105: 16671-16676.
111. Kosmrlj, A., E. L. Read, Y. Qi, T. M. Allen, M. Altfeld, S. G. Deeks, F. Pereyra, M. Carrington, B. D. Walker, and A. K. Chakraborty. 2010. Effects of thymic selection of the T-cell repertoire on HLA class I-associated control of HIV infection. Nature 465: 350-354.