Journal of Experimental Medicine, Vol 175, 481-487, Copyright © 1992 by Rockefeller University Press

ARTICLES

Flanking sequences influence the presentation of an endogenously synthesized peptide to cytotoxic T lymphocytes

LC Eisenlohr, JW Yewdell and JR Bennink
Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892.

Cytotoxic T lymphocytes (CTL) recognize class I major histocompatibility complex molecules complexed to peptides of eight to nine residues generated from cytosolic proteins. We find that CTL recognize, in vitro and in vivo, cells synthesizing a 10-residue peptide consisting of an initiating methionine followed by nine residues corresponding to a naturally processed determinant from influenza virus nucleoprotein (NP) (residues 147-155). Addition of two COOH-terminal residues corresponding to NP residues 157 and 158 severely reduced presentation of the endogenously produced peptide to CTL in vitro and in vivo. Extension of NH2 and COOH terminal flanking residues to include residues corresponding to NP residues 137-146 and 159-168 failed to increase the antigenicity of this peptide. Its presentation was greatly enhanced, however, by further extending the NH2 and COOH termini to include all of the additional residues of NP. These findings indicate first, that a naturally processed viral ligand (with an NH2-terminal Met) of a class I molecule contains sufficient information to access intracellular class I molecules, and second, that flanking residues can influence the processing and presentation of antigens to CTL.
CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Johnstone, C., Guil, S., Rico, M. A., Garcia-Barreno, B., Lopez, D., Melero, J. A., Del Val, M. (2008). Relevance of viral context and diversity of antigen-processing routes for respiratory syncytial virus cytotoxic T-lymphocyte epitopes. J. Gen. Virol. 89: 2194-2203 [Abstract] [Full Text]  
• May, R. J., Dao, T., Pinilla-Ibarz, J., Korontsvit, T., Zakhaleva, V., Zhang, R. H., Maslak, P., Scheinberg, D. A. (2007). Peptide Epitopes from the Wilms' Tumor 1 Oncoprotein Stimulate CD4+ and CD8+ T Cells That Recognize and Kill Human Malignant Mesothelioma Tumor Cells. Clin. Cancer Res. 13: 4547-4555 [Abstract] [Full Text]  
• Pang, K. C., Sanders, M. T., Monaco, J. J., Doherty, P. C., Turner, S. J., Chen, W. (2006). Immunoproteasome Subunit Deficiencies Impact Differentially on Two Immunodominant Influenza Virus-Specific CD8+ T Cell Responses. J. Immunol. 177: 7680-7688 [Abstract] [Full Text]  
• Zook, M. B., Howard, M. T., Sinnathamby, G., Atkins, J. F., Eisenlohr, L. C. (2006). Epitopes Derived by Incidental Translational Frameshifting Give Rise to a Protective CTL Response.. J. Immunol. 176: 6928-6934 [Abstract] [Full Text]  
• Thilo, C., Berglund, P., Applequist, S. E., Yewdell, J. W., Ljunggren, H.-G., Achour, A. (2006). Dissection of the Interaction of the Human Cytomegalovirus-derived US2 Protein with Major Histocompatibility Complex Class I Molecules: PROMINENT ROLE OF A SINGLE ARGININE RESIDUE IN HUMAN LEUKOCYTE ANTIGEN-A2. J. Biol. Chem. 281: 8950-8957 [Abstract] [Full Text]  
• La Gruta, N. L., Kedzierska, K., Pang, K., Webby, R., Davenport, M., Chen, W., Turner, S. J., Doherty, P. C. (2006). A virus-specific CD8+ T cell immunodominance hierarchy determined by antigen dose and precursor frequencies. Proc. Natl. Acad. Sci. USA 103: 994-999 [Abstract] [Full Text]  
• Bruder, D., Nussbaum, A. K., Gakamsky, D. M., Schirle, M., Stevanovic, S., Singh-Jasuja, H., Darji, A., Chakraborty, T., Schild, H., Pecht, I., Weiss, S. (2006). Multiple synergizing factors contribute to the strength of the CD8+ T cell response against listeriolysin O. Int Immunol 18: 89-100 [Abstract] [Full Text]  
• Milicic, A., Price, D. A., Zimbwa, P., Booth, B. L., Brown, H. L., Easterbrook, P. J., Olsen, K., Robinson, N., Gileadi, U., Sewell, A. K., Cerundolo, V., Phillips, R. E. (2005). CD8+ T Cell Epitope-Flanking Mutations Disrupt Proteasomal Processing of HIV-1 Nef. J. Immunol. 175: 4618-4626 [Abstract] [Full Text]  
• Crowe, S. R., Miller, S. C., Shenyo, R. M., Woodland, D. L. (2005). Vaccination with an Acidic Polymerase Epitope of Influenza Virus Elicits a Potent Antiviral T Cell Response but Delayed Clearance of an Influenza Virus Challenge. J. Immunol. 174: 696-701 [Abstract] [Full Text]  
• Johnstone, C., de Leon, P., Medina, F., Melero, J. A., Garcia-Barreno, B., Val, M. D. (2004). Shifting immunodominance pattern of two cytotoxic T-lymphocyte epitopes in the F glycoprotein of the Long strain of respiratory syncytial virus. J. Gen. Virol. 85: 3229-3238 [Abstract] [Full Text]  
• Purcell, A. W., Gorman, J. J. (2004). Immunoproteomics: Mass Spectrometry-based Methods to Study the Targets of the Immune Response. Mol. Cell. Proteomics 3: 193-208 [Abstract] [Full Text]  
• Yang, A. S., Monken, C. E., Lattime, E. C. (2003). Intratumoral Vaccination with Vaccinia-Expressed Tumor Antigen and Granulocyte Macrophage Colony-Stimulating Factor Overcomes Immunological Ignorance to Tumor Antigen. Cancer Res. 63: 6956-6961 [Abstract] [Full Text]  
• Crowe, S. R., Turner, S. J., Miller, S. C., Roberts, A. D., Rappolo, R. A., Doherty, P. C., Ely, K. H., Woodland, D. L. (2003). Differential Antigen Presentation Regulates the Changing Patterns of CD8+ T Cell Immunodominance in Primary and Secondary Influenza Virus Infections. J. Exp. Med. 198: 399-410 [Abstract] [Full Text]  
• Migueles, S. A., Laborico, A. C., Imamichi, H., Shupert, W. L., Royce, C., McLaughlin, M., Ehler, L., Metcalf, J., Liu, S., Hallahan, C. W., Connors, M. (2003). The Differential Ability of HLA B*5701+ Long-Term Nonprogressors and Progressors To Restrict Human Immunodeficiency Virus Replication Is Not Caused by Loss of Recognition of Autologous Viral gag Sequences. J. Virol. 77: 6889-6898 [Abstract] [Full Text]  
• Powell, D. J. Jr., Eisenlohr, L. C., Rothstein, J. L. (2003). A Thyroid Tumor-Specific Antigen Formed by the Fusion of Two Self Proteins. J. Immunol. 170: 861-869 [Abstract] [Full Text]  
• Probst, H. C., Dumrese, T., van den Broek, M. F. (2002). Cutting Edge: Competition for APC by CTLs of Different Specificities Is Not Functionally Important During Induction of Antiviral Responses. J. Immunol. 168: 5387-5391 [Abstract] [Full Text]  
• Currier, J. R., deSouza, M., Chanbancherd, P., Bernstein, W., Birx, D. L., Cox, J. H. (2002). Comprehensive Screening for Human Immunodeficiency Virus Type 1 Subtype-Specific CD8 Cytotoxic T Lymphocytes and Definition of Degenerate Epitopes Restricted by HLA-A0207 and -CW0304 Alleles. J. Virol. 76: 4971-4986 [Abstract] [Full Text]  
• Rodriguez, F., Harkins, S., Slifka, M. K., Whitton, J. L. (2002). Immunodominance in Virus-Induced CD8+ T-Cell Responses Is Dramatically Modified by DNA Immunization and Is Regulated by Gamma Interferon. J. Virol. 76: 4251-4259 [Abstract] [Full Text]  
• Rich, R. F., Green, W. R. (2002). Characterization of the Fas Ligand/Fas-Dependent Apoptosis of Antiretroviral, Class I MHC Tetramer-Defined, CD8+ CTL by In Vivo Retrovirus-Infected Cells. J. Immunol. 168: 2751-2758 [Abstract] [Full Text]  
• Rasmussen, I. B., Lunde, E., Michaelsen, T. E., Bogen, B., Sandlie, I. (2001). The principle of delivery of T cell epitopes to antigen-presenting cells applied to peptides from influenza virus, ovalbumin, and hen egg lysozyme: Implications for peptide vaccination. Proc. Natl. Acad. Sci. USA 10.1073/pnas.181336898v1 [Abstract] [Full Text]  
• Moreau-Aubry, A., Le Guiner, S., Labarriere, N., Gesnel, M.-C., Jotereau, F., Breathnach, R. (2000). A Processed Pseudogene Codes for a New Antigen Recognized by a CD8+ T Cell Clone on Melanoma. J. Exp. Med. 191: 1617-1624 [Abstract] [Full Text]  
• Sevilla, N., Homann, D., von Herrath, M., Rodriguez, F., Harkins, S., Whitton, J. L., Oldstone, M. B. A. (2000). Virus-Induced Diabetes in a Transgenic Model: Role of Cross-Reacting Viruses and Quantitation of Effector T Cells Needed To Cause Disease. J. Virol. 74: 3284-3292 [Abstract] [Full Text]  
• Beekman, N. J., van Veelen, P. A., van Hall, T., Neisig, A., Sijts, A., Camps, M., Kloetzel, P.-M., Neefjes, J. J., Melief, C. J., Ossendorp, F. (2000). Abrogation of CTL Epitope Processing by Single Amino Acid Substitution Flanking the C-Terminal Proteasome Cleavage Site. J. Immunol. 164: 1898-1905 [Abstract] [Full Text]  
• Brander, C., Yang, O. O., Jones, N. G., Lee, Y., Goulder, P., Johnson, R. P., Trocha, A., Colbert, D., Hay, C., Buchbinder, S., Bergmann, C. C., Zweerink, H. J., Wolinsky, S., Blattner, W. A., Kalams, S. A., Walker, B. D. (1999). Efficient Processing of the Immunodominant, HLA-A*0201-Restricted Human Immunodeficiency Virus Type 1 Cytotoxic T-Lymphocyte Epitope despite Multiple Variations in the Epitope Flanking Sequences. J. Virol. 73: 10191-10198 [Abstract] [Full Text]  
• Wherry, E. J., Puorro, K. A., Porgador, A., Eisenlohr, L. C. (1999). The Induction of Virus-Specific CTL as a Function of Increasing Epitope Expression: Responses Rise Steadily Until Excessively High Levels of Epitope Are Attained. J. Immunol. 163: 3735-3745 [Abstract] [Full Text]  
• Montoya, M., Del Val, M. (1999). Intracellular Rate-Limiting Steps in MHC Class I Antigen Processing. J. Immunol. 163: 1914-1922 [Abstract] [Full Text]  
• Mylin, L. M. (1999). Context-Dependent Immunogenicity of an S206G-Substituted H-2Db-Restricted Simian Virus 40 Large T Antigen Epitope I Variant. J. Immunol. 162: 2171-2179 [Abstract] [Full Text]  
• Riberdy, J. M., Flynn, K. J., Stech, J., Webster, R. G., Altman, J. D., Doherty, P. C. (1999). Protection against a Lethal Avian Influenza A Virus in a Mammalian System. J. Virol. 73: 1453-1459 [Abstract] [Full Text]  
• Theobald, M., Ruppert, T., Kuckelkorn, U., Hernandez, J., Haussler, A., Ferreira, E. A., Liewer, U., Biggs, J., Levine, A. J., Huber, C., Koszinowski, U. H., Kloetzel, P.-M., Sherman, L. A. (1998). The Sequence Alteration Associated with a Mutational Hotspot in p53 Protects Cells From Lysis by Cytotoxic T Lymphocytes Specific for a Flanking Peptide Epitope. J. Exp. Med. 188: 1017-1028 [Abstract] [Full Text]  
• Mata, M., Travers, P. J., Liu, Q., Frankel, F. R., Paterson, Y. (1998). The MHC Class I-Restricted Immune Response to HIV-gag in BALB/c Mice Selects a Single Epitope That Does Not Have a Predictable MHC-Binding Motif and Binds to Kd Through Interactions Between a Glutamine at P3 and Pocket D. J. Immunol. 161: 2985-2993 [Abstract] [Full Text]  
• Vijh, S., Pilip, I. M., Pamer, E. G. (1998). Effect of Antigen-Processing Efficiency on In Vivo T Cell Response Magnitudes. J. Immunol. 160: 3971-3977 [Abstract] [Full Text]  
• Kulig, K., Nandi, D., Bacik, I., Monaco, J. J., Vukmanovic, S. (1998). Physical and Functional Association of the Major Histocompatibility Complex Class I Heavy Chain alpha 3 Domain with the Transporter Associated with Antigen Processing. J. Exp. Med. 187: 865-874 [Abstract] [Full Text]  
• Bertoletti, A., Cham, F., McAdam, S., Rostron, T., Rowland-Jones, S., Sabally, S., Corrah, T., Ariyoshi, K., Whittle, H. (1998). Cytotoxic T Cells from Human Immunodeficiency Virus Type 2-Infected Patients Frequently Cross-React with Different Human Immunodeficiency Virus Type 1 Clades. J. Virol. 72: 2439-2448 [Abstract] [Full Text]  
• Mortara, L., Letourneur, F., Gras-masse, H., Venet, A., Guillet, J.-G., Bourgault-Villada, I. (1998). Selection of Virus Variants and Emergence of Virus Escape Mutants after Immunization with an Epitope Vaccine. J. Virol. 72: 1403-1410 [Abstract] [Full Text]  
• Fu, T.-M., Mylin, L. M., Schell, T. D., Bacik, I., Russ, G., Yewdell, J. W., Bennink, J. R., Tevethia, S. S. (1998). An Endoplasmic Reticulum-Targeting Signal Sequence Enhances the Immunogenicity of an Immunorecessive Simian Virus 40 Large T Antigen Cytotoxic T-Lymphocyte Epitope. J. Virol. 72: 1469-1481 [Abstract] [Full Text]  
• Bullock, T. N.J., Patterson, A. E., Franlin, L. L., Notidis, E., Eisenlohr, L. C. (1997). Initiation Codon Scanthrough versus Termination Codon Readthrough Demonstrates Strong Potential for Major Histocompatibility Complex Class I-restricted Cryptic Epitope Expression. J. Exp. Med. 186: 1051-1058 [Abstract] [Full Text]  
• Ahlers, J. D., Takeshita, T., Pendleton, C. D., Berzofsky, J. A. (1997). Enhanced immunogenicity of HIV-1 vaccine construct by modification of the native peptide sequence. Proc. Natl. Acad. Sci. USA 94: 10856-10861 [Abstract] [Full Text]  
• Miconnet, I., Servis, C., Cerottini, J.-C., Romero, P., Levy, F. (2000). Amino Acid Identity and/or Position Determines the Proteasomal Cleavage of the HLA-A*0201-restricted Peptide Tumor Antigen MAGE-3271-279. J. Biol. Chem. 275: 26892-26897 [Abstract] [Full Text]  
• Rasmussen, I. B., Lunde, E., Michaelsen, T. E., Bogen, B., Sandlie, I. (2001). The principle of delivery of T cell epitopes to antigen-presenting cells applied to peptides from influenza virus, ovalbumin, and hen egg lysozyme: Implications for peptide vaccination. Proc. Natl. Acad. Sci. USA 98: 10296-10301 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS