The Journal of Immunology, Vol 152, Issue 1 163-175, Copyright © 1994 by American Association of Immunologists

ARTICLES

Scheme for ranking potential HLA-A2 binding peptides based on independent binding of individual peptide side-chains

KC Parker, MA Bednarek and JE Coligan
Biological Resources Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892.

A method to predict the relative binding strengths of all possible nonapeptides to the MHC class I molecule HLA-A2 has been developed based on experimental peptide binding data. These data indicate that, for most peptides, each side-chain of the peptide contributes a certain amount to the stability of the HLA-A2 complex that is independent of the sequence of the peptide. To quantify these contributions, the binding data from a set of 154 peptides were combined together to generate a table containing 180 coefficients (20 amino acids x 9 positions), each of which represents the contribution of one particular amino acid residue at a specified position within the peptide to binding to HLA-A2. Eighty peptides formed stable HLA-A2 complexes, as assessed by measuring the rate of dissociation of beta 2m. The remaining 74 peptides formed complexes that had a half-life of beta 2m dissociation of less than 5 min at 37 degrees C, or did not bind to HLA- A2, and were included because they could be used to constrain the values of some of the coefficients. The "theoretical" binding stability (calculated by multiplying together the corresponding coefficients) matched the experimental binding stability to within a factor of 5. The coefficients were then used to calculate the theoretical binding stability for all the previously identified self or antigenic nonamer peptides known to bind to HLA-A2. The binding stability for all other nonamer peptides that could be generated from the proteins from which these peptides were derived was also predicted. In every case, the previously described HLA-A2 binding peptides were ranked in the top 2% of all possible nonamers for each source protein. Therefore, most biologically relevant nonamer peptides should be identifiable using the table of coefficients. We conclude that the side-chains of most nonamer peptides to the first approximation bind independently of one another to the HLA-A2 molecule.

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				J. Yokokawa, C. Palena, P. Arlen, R. Hassan, M. Ho, I. Pastan, J. Schlom, and K. Y. Tsang Identification of Novel Human CTL Epitopes and Their Agonist Epitopes of Mesothelin Clin. Cancer Res., September 1, 2005; 11(17): 6342 - 6351. [Abstract] [Full Text] [PDF]

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				N. Harashima, R. Tanosaki, Y. Shimizu, K. Kurihara, T. Masuda, J. Okamura, and M. Kannagi Identification of Two New HLA-A*1101-Restricted Tax Epitopes Recognized by Cytotoxic T Lymphocytes in an Adult T-Cell Leukemia Patient after Hematopoietic Stem Cell Transplantation J. Virol., August 1, 2005; 79(15): 10088 - 10092. [Abstract] [Full Text] [PDF]

				C. E. Clark and R. H. Vonderheide Getting to the Surface: A Link Between Tumor Antigen Discovery and Natural Presentation of Peptide-MHC Complexes Clin. Cancer Res., August 1, 2005; 11(15): 5333 - 5336. [Full Text] [PDF]

				J. Greiner, L. Li, M. Ringhoffer, T. F. E. Barth, K. Giannopoulos, P. Guillaume, G. Ritter, M. Wiesneth, H. Dohner, and M. Schmitt Identification and characterization of epitopes of the receptor for hyaluronic acid-mediated motility (RHAMM/CD168) recognized by CD8+ T cells of HLA-A2-positive patients with acute myeloid leukemia Blood, August 1, 2005; 106(3): 938 - 945. [Abstract] [Full Text] [PDF]

				P. Correale*, M. G. Cusi, M. T. Del Vecchio, A. Aquino, S. Prete, K. Y. Tsang, L. Micheli, C. Nencini, M. La Placa*, F. Montagnani*, et al. Dendritic Cell-Mediated Cross-Presentation of Antigens Derived from Colon Carcinoma Cells Exposed to a Highly Cytotoxic Multidrug Regimen with Gemcitabine, Oxaliplatin, 5-Fluorouracil, and Leucovorin, Elicits a Powerful Human Antigen-Specific CTL Response with Antitumor Activity in Vitro J. Immunol., July 15, 2005; 175(2): 820 - 828. [Abstract] [Full Text] [PDF]

				C. Lotz, S. A. Mutallib, N. Oehlrich, U. Liewer, E. A. Ferreira, M. Moos, M. Hundemer, S. Schneider, S. Strand, C. Huber, et al. Targeting Positive Regulatory Domain I-Binding Factor 1 and X Box-Binding Protein 1 Transcription Factors by Multiple Myeloma-Reactive CTL J. Immunol., July 15, 2005; 175(2): 1301 - 1309. [Abstract] [Full Text] [PDF]

				Y. Nagata, T. Hanagiri, M. Takenoyama, T. Fukuyama, M. Mizukami, T. So, Y. Ichiki, M. Sugaya, K. Sugio, and K. Yasumoto Identification of the HLA-Cw*0702-Restricted Tumor-Associated Antigen Recognized by a CTL Clone from a Lung Cancer Patient Clin. Cancer Res., July 15, 2005; 11(14): 5265 - 5272. [Abstract] [Full Text] [PDF]

				R. J. P. Brown, V. S. Juttla, A. W. Tarr, R. Finnis, W. L. Irving, S. Hemsley, D. R. Flower, P. Borrow, and J. K. Ball Evolutionary dynamics of hepatitis C virus envelope genes during chronic infection J. Gen. Virol., July 1, 2005; 86(7): 1931 - 1942. [Abstract] [Full Text] [PDF]

				Y. Hassainya, F. Garcia-Pons, R. Kratzer, V. Lindo, F. Greer, F. A. Lemonnier, G. Niedermann, and P. M. van Endert Identification of Naturally Processed HLA-A2--Restricted Proinsulin Epitopes by Reverse Immunology Diabetes, July 1, 2005; 54(7): 2053 - 2059. [Abstract] [Full Text] [PDF]

				G. L. Zhang, A. M. Khan, K. N. Srinivasan, J. T. August, and V. Brusic MULTIPRED: a computational system for prediction of promiscuous HLA binding peptides Nucleic Acids Res., July 1, 2005; 33(suppl_2): W172 - W179. [Abstract] [Full Text] [PDF]

				G. L. Zhang, K. N. Srinivasan, A. Veeramani, J. T. August, and V. Brusic PREDBALB/c: a system for the prediction of peptide binding to H2d molecules, a haplotype of the BALB/c mouse Nucleic Acids Res., July 1, 2005; 33(suppl_2): W180 - W183. [Abstract] [Full Text] [PDF]

				J. Dupont, J.-B. Latouche, C. Ma, and M. Sadelain Artificial Antigen-Presenting Cells Transduced with Telomerase Efficiently Expand Epitope-Specific, Human Leukocyte Antigen-Restricted Cytotoxic T Cells Cancer Res., June 15, 2005; 65(12): 5417 - 5427. [Abstract] [Full Text] [PDF]

				D. A. Rodeberg, R. A. Nuss, S. F. Elsawa, and E. Celis Recognition of Six-Transmembrane Epithelial Antigen of the Prostate-Expressing Tumor Cells by Peptide Antigen-Induced Cytotoxic T Lymphocytes Clin. Cancer Res., June 15, 2005; 11(12): 4545 - 4552. [Abstract] [Full Text] [PDF]

				S. Wada, T. Tsunoda, T. Baba, F. J. Primus, H. Kuwano, M. Shibuya, and H. Tahara Rationale for Antiangiogenic Cancer Therapy with Vaccination Using Epitope Peptides Derived from Human Vascular Endothelial Growth Factor Receptor 2 Cancer Res., June 1, 2005; 65(11): 4939 - 4946. [Abstract] [Full Text] [PDF]

				A. Bredenbeck, F. O. Losch, T. Sharav, M. Eichler-Mertens, M. Filter, A. Givehchi, W. Sterry, P. Wrede, and P. Walden Identification of Noncanonical Melanoma-Associated T Cell Epitopes for Cancer Immunotherapy J. Immunol., June 1, 2005; 174(11): 6716 - 6724. [Abstract] [Full Text] [PDF]

				M. G. Cusi, M. T. Del Vecchio, C. Terrosi, G. G. Savellini, G. Di Genova, M. La Placa, F. Fallarino, C. Moser, C. Cardone, G. Giorgi, et al. Immune-Reconstituted Influenza Virosome Containing CD40L Gene Enhances the Immunological and Protective Activity of a Carcinoembryonic Antigen Anticancer Vaccine J. Immunol., June 1, 2005; 174(11): 7210 - 7216. [Abstract] [Full Text] [PDF]

				F. van Rhee, S. M. Szmania, F. Zhan, S. K. Gupta, M. Pomtree, P. Lin, R. B. Batchu, A. Moreno, G. Spagnoli, J. Shaughnessy, et al. NY-ESO-1 is highly expressed in poor-prognosis multiple myeloma and induces spontaneous humoral and cellular immune responses Blood, May 15, 2005; 105(10): 3939 - 3944. [Abstract] [Full Text] [PDF]

				A. Chen, L. Wang, J. Zhang, L. Zou, Z. Jia, W. Zhou, Y. Wan, and Y. Wu H-2 Kd-Restricted Hepatitis B Virus-Derived Epitope Whose Specific CD8+ T Lymphocytes Can Produce Gamma Interferon without Cytotoxicity J. Virol., May 1, 2005; 79(9): 5568 - 5576. [Abstract] [Full Text] [PDF]

				K. L. Bondurant, M. D. Crew, A. D. Santin, T. J. O'Brien, and M. J. Cannon Definition of an Immunogenic Region Within the Ovarian Tumor Antigen Stratum Corneum Chymotryptic Enzyme Clin. Cancer Res., May 1, 2005; 11(9): 3446 - 3454. [Abstract] [Full Text] [PDF]

				D. Trivedi, R. Y. Williams, R. J. O'Reilly, and G. Koehne Generation of CMV-specific T lymphocytes using protein-spanning pools of pp65-derived overlapping pentadecapeptides for adoptive immunotherapy Blood, April 1, 2005; 105(7): 2793 - 2801. [Abstract] [Full Text] [PDF]

				V. A. Pudney, A. M. Leese, A. B. Rickinson, and A. D. Hislop CD8+ immunodominance among Epstein-Barr virus lytic cycle antigens directly reflects the efficiency of antigen presentation in lytically infected cells J. Exp. Med., February 7, 2005; 201(3): 349 - 360. [Abstract] [Full Text] [PDF]

				R. Varela-Calvino, A. Skowera, S. Arif, and M. Peakman Identification of a Naturally Processed Cytotoxic CD8 T-Cell Epitope of Coxsackievirus B4, Presented by HLA-A2.1 and Located in the PEVKEK Region of the P2C Nonstructural Protein J. Virol., December 15, 2004; 78(24): 13399 - 13408. [Abstract] [Full Text] [PDF]