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

Journal of Virology

Volumn 81, Issue 14, 2007, Pages 7608-7619

  Richards, Katherine A ^a   Chaves, Francisco A ^a   Krafcik, Frederick R ^a   Topham, David J ^a   Lazarski, Christopher A ^a   Sant, Andrea J ^a  

^a UNIVERSITY OF ROCHESTER MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPITOPE; HLA DR1 ANTIGEN; VIRUS HEMAGGLUTININ;

ALGORITHM; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CD4+ T LYMPHOCYTE; CELLULAR IMMUNITY; COMPARATIVE STUDY; CONTROLLED STUDY; ENDEMIC DISEASE; EX VIVO STUDY; INFLUENZA; INFLUENZA VIRUS; MOUSE; NONHUMAN; PRIORITY JOURNAL; TRANSGENIC MOUSE; VIRUS IMMUNITY; VIRUS STRAIN; VIRUS TYPING;

AMINO ACID SEQUENCE; ANIMALS; CD4-POSITIVE T-LYMPHOCYTES; CELL LINE; ENZYME-LINKED IMMUNOSORBENT ASSAY; HEMAGGLUTININS, VIRAL; HLA-DR1 ANTIGEN; MICE; MICE, TRANSGENIC; MOLECULAR SEQUENCE DATA; ORTHOMYXOVIRIDAE; SEQUENCE HOMOLOGY, AMINO ACID;

AVES; INFLUENZA A VIRUS; MUS MUSCULUS; ORTHOMYXOVIRIDAE;

EID: 34447250320     PISSN: 0022538X     EISSN: None     Source Type: Journal    
DOI: 10.1128/JVI.02834-06     Document Type: Article

References (114)

1. Al-Attiyah, R., and A. S. Mustafa. 2004. Computer-assisted prediction of HLA-DR binding and experimental analysis for human promiscuous Th1-cell peptides in the 24 kDa secreted lipoprotein (LppX) of Mycobacterium tuberculosis. Scand. J. Immunol. 59:16-24.
2. Anthony, D. D., and P. V. Lehmann. 2003. T-cell epitope mapping using the ELISPOT approach. Methods 29:260-269.
3. Barnett, B. C., D. S. Burt, C. M. Graham, A. P. Warren, J. J. Skehel, and D. B. Thomas. 1989. I-Ad restricted T cell recognition of influenza hemagglutinin. Synthetic peptides identify multiple epitopes corresponding to antibody-binding regions of the HA1 subunit. J. Immunol. 143:2663-2669.
4. Bender, A., M. Albert, A. Reddy, M. Feldman, B. Sauter, G. Kaplan, W. Hellman, and N. Bhardwaj. 1998. The distinctive features of influenza virus infection of dendritic cells. Immunobiology 198:552-567.
5. + T cells. J. Clin. Investig. 94:797-807.
6. Blum, J. S., C. Ma, and S. Kovats. 1997. Antigen-presenting cells and the selection of immunodominant epitopes. Crit. Rev. Immunol. 17:411-417.
7. Brown, D. M., E. Roman, and S. L. Swain. 2004. CD4 T cell responses to influenza infection. Semin. Immunol. 16:171-177.
8. Brown, L. R., N. R. Nygard, M. B. Graham, C. Bono, V. L. Braciale, J. Gorka, B. D. Schwartz, and T. J. Braciale. 1991. Recognition of the influenza hemagglutinin by class II MHC-restricted T lymphocytes and antibodies. I. Site definition and implications for antigen presentation and T lymphocyte recognition. J. Immunol. 147:2677-2684.
9. Brusic, V., V. B. Bajic, and N. Petrovsky. 2004. Computational methods for prediction of T-cell epitopes: a framework for modelling, testing, and applications. Methods 34:436-443.
10. Bui, H. H., J. Sidney, K. Dinh, S. Southwood, M. J. Newman, and A. Sette. 2006. Predicting population coverage of T-cell epitope-based diagnostics and vaccines. BMC Bioinformatics 7:153.
11. Busch, R., C. H. Rinderknecht, S. Roh, A. W. Lee, J. J. Harding, T. Burster, T. M. Hornell, and E. D. Mellins. 2005. Achieving stability through editing and chaperoning: regulation of MHC class II peptide binding and expression. Immunol. Rev. 207:242-260.
12. Canaday, D. H., A. Gehring, E. G. Leonard, B. Eilertson, J. R. Schreiber, C. V. Harding, and W. H. Boom. 2003. T-cell hybridomas from HLA-transgenic mice as tools for analysis of human antigen processing. J. Immunol. Methods 281:129-142.
13. Capua, I., and D. J. Alexander. 2004. Human health implications of avian influenza viruses and paramyxoviruses. Eur. J. Clin. Microbiol. Infect. Dis. 23:1-6.
14. 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.
15. Couch, R. B. 2003. An overview of serum antibody responses to influenza virus antigens. Dev. Biol. 115:25-30.
16. Crowe, S. R., S. C. Miller, D. M. Brown, P. S. Adams, R. W. Dutton, A. G. Harmsen, F. E. Lund, T. D. Randall, S. L. Swain, and D. L. Woodland. 2006. Uneven distribution of MHC class II epitopes within the influenza virus. Vaccine 24:457-467.
17. Dawson, D. V., M. Ozgur, K. Sari, M. Ghanayem, and D. D. Kostyu. 2001. Ramifications of HLA class I polymorphism and population genetics for vaccine development. Genet. Epidemiol. 20:87-106.
18. Depil, S., G. Angyalosi, O. Morales, M. Delacre, N. Delhem, V. Francois, B. Georges, J. Hammer, B. Maillere, C. Auriault, and V. Pancre. 2006. Peptide-binding assays and HLA II transgenic Abeta degrees mice are consistent and complementary tools for identifying HLA II-restricted peptides. Vaccine 24:2225-2229.
19. + T cell memory. Immunol. Rev. 150:23-44.
20. Doytchinova, I. A., and D. R. Flower. 2005. In silico identification of super-types for class II MHCs. J. Immunol. 174:7085-7095.
21. Draenert, R., M. Altfeld, C. Brander, N. Basgoz, C. Corcoran, A. G. Wurcel, D. R. Stone, S. A. Kalams, A. Trocha, M. M. Addo, P. J. Goulder, and B. D. Walker. 2003. Comparison of overlapping peptide sets for detection of antiviral CD8 and CD4 T cell responses. J. Immunol. Methods 275:19-29.
22. Fleischer, B., H. Becht, and R. Rott. 1985. Recognition of viral antigens by human influenza A virus-specific T lymphocyte clones. J. Immunol. 135:2800-2804.
23. Geginat, G., S. Schenk, M. Skoberne, W. Goebel, and H. Hof. 2001. A novel approach of direct ex vivo epitope mapping identifies dominant and sub-dominant CD4 and CD8 T cell epitopes from Listeria monocytogenes. J. Immunol. 166:1877-1884.
24. Gelder, C., M. Davenport, M. Barnardo, T. Bourne, J. Lamb, B. Askonas, A. Hill, and K. Welsh. 1998. Six unrelated HLA-DR-matched adults recognize identical CD4+ T cell epitopes from influenza A haemagglutinin that are not simply peptides with high HLA-DR binding affinities. Int. Immunol. 10:211-222.
25. + T-cell recognition of influenza A virus hemagglutinin after subunit vaccination. J. Virol. 70:4787-4790.
26. + T-cell repertoire of responses to influenza A virus hemagglutinin after recent natural infection. J. Virol. 69:7497-7506.
27. Gerdil, C. 2003. The annual production cycle for influenza vaccine. Vaccine 21:1776-1779.
28. Gerdil, C. 2003. Using the strains and getting the vaccine licensed: a vaccine manufacturer's view. Dev. Biol. (Basel) 115:17-21.
29. Gerhard, W. 2001. The role of the antibody response in influenza virus infection. Curr. Top. Microbiol. Immunol. 260:171-190.
30. Gillim-Ross, L., and K. Subbarao. 2006. Emerging respiratory viruses: challenges and vaccine strategies. Clin. Microbiol. Rev. 19:614-636.
31. Gillis, J. S. 2006. An avian influenza vaccine for humans targeting the polymerase B2 protein inside the capsid instead of hemagglutinin or neuramidase on the virus surface. Med. Hypotheses 66:975-977.
32. Gomez-Nunez, M., J. Pinilla-Ibarz, T. Dao, R. J. May, M. Pao, J. S. Jaggi, and D. A. Scheinberg. 2006. Peptide binding motif predictive algorithms correspond with experimental binding of leukemia vaccine candidate peptides to HLA-A*0201 molecules. Leuk. Res. 30:1293-1298.
33. Greenstein, J. L., V. C. Schad, W. H. Goodwin, A. B. Brauer, B. K. Bollinger, R. D. Chin, and M. C. Kuo. 1992. A universal T cell epitope-containing peptide from hepatitis B surface antigen can enhance antibody specific for HIV gp120. J. Immunol. 148:3970-3977.
34. Hamilton-Easton, A., and M. Eichelberger. 1995. Virus-specific antigen presentation by different subsets of cells from lung and mediastinal lymph node tissues of influenza virus-infected mice. J. Virol. 69:6359-6366.
35. Hansson, L., H. Rabbani, J. Fagerberg, A. Osterborg, and H. Mellstedt. 2003. T-cell epitopes within the complementarity-determining and framework regions of the tumor-derived immunoglobulin heavy chain in multiple myeloma. Blood 101:4930-4936.
36. He, X., E. F. Rosloniec, L. K. Myers, W. L. McColgan III, M. Gumanovskaya, A. H. Kang, and J. M. Stuart. 2004. T cell receptors recognizing type II collagen in HLA-DR-transgenic mice characterized by highly restricted V beta usage. Arthritis Rheum. 50:1996-2004.
37. Hilleman, M. R. 2002. Realities and enigmas of human viral influenza: pathogenesis, epidemiology and control. Vaccine 20:3068-3087.
38. Hobeika, A. C., M. A. Morse, T. Osada, M. Ghanayem, D. Niedzwiecki, R. Barrier, H. K. Lyerly, and T. M. Clay. 2005. Enumerating antigen-specific T-cell responses in peripheral blood: a comparison of peptide MHC Tetramer, ELISpot, and intracellular cytokine analysis. J. Immunother. 28:63-72.
39. Hunziker, I. P., R. Zurbriggen, R. Glueck, O. B. Engler, J. Reichen, W. J. Dai, W. J. Pichler, and A. Cerny. 2001. Perspectives: towards a peptide-based vaccine against hepatitis C virus. Mol. Immunol. 38:475-484.
40. Iwai, L. K., M. Yoshida, J. Sidney, M. A. Shikanai-Yasuda, A. C. Goldberg, M. A. Juliano, J. Hammer, L. Juliano, A. Sette, J. Kalil, L. R. Travassos, and E. Cunha-Neto. 2003. In silico prediction of peptides binding to multiple HLA-DR molecules accurately identifies immunodominant epitopes from gp43 of Paracoccidioides brasiliensis frequently recognized in primary peripheral blood mononuclear cell responses from sensitized individuals. Mol. Med. 9:209-219.
41. + T-cell memory via TRAIL-mediated activation-induced cell death. Nature 434:88-93.
42. + T lymphocytes. Nature 421:852-856.
43. Jensen, P. E., D. A. Weber, W. P. Thayer, X. Chen, and C. T. Dao. 1999. HLA-DM and the MHC class II antigen presentation pathway. Immunol. Res. 20:195-205.
44. Joseph, T., and K. Subbarao. 2005. Human infections with avian influenza viruses. Maryland Med. 6:30-32.
45. Karlsson, A. C., J. N. Martin, S. R. Younger, B. M. Bredt, L. Epling, R. Ronquillo, A. Varma, S. G. Deeks, J. M. McCune, D. F. Nixon, and E. Sinclair. 2003. Comparison of the ELISPOT and cytokine flow cytometry assays for the enumeration of antigen-specific T cells. J. Immunol. Methods 283:141-153.
46. Katz, J. M., J. Plowden, M. Renshaw-Hoelscher, X. Lu, T. M. Tumpey, and S. Sambhara. 2004. Immunity to influenza: the challenges of protecting an aging population. Immunol. Res. 29:113-124.
47. Kedl, R. M., J. W. Kappler, and P. Marrack. 2003. Epitope dominance, competition and T cell affinity maturation. Curr. Opin. Immunol. 15:120-127.
48. Khanolkar, A., M. J. Fuller, and A. J. Zajac. 2004. CD4 T cell-dependent CD8 T cell maturation. J. Immunol. 172:2834-2844.
49. Kitler, M. E., P. Gavinio, and D. Lavanchy. 2002. Influenza and the work of the World Health Organization. Vaccine 20(Suppl. 2):S5-S14.
50. Kobasa, D., and Y. Kawaoka. 2005. Emerging influenza viruses: past and present. Curr. Mol. Med. 5:791-803.
51. Kropshofer, H., A. B. Vogt, G. Moldenhauer, J. Hammer, J. S. Blum, and G. J. Hammerling. 1996. Editing of the HLA-DR-peptide repertoire by HLA-DM. EMBO J. 15:6144-6154.
52. + T cells. J. Immunol. Methods 268:71-81.
53. Lamb, J. R., D. D. Eckels, M. Phelan, P. Lake, and J. N. Woody. 1982. Antigen-specific human T lymphocyte clones: viral antigen specificity of influenza virus-immune clones. J. Immunol. 128:1428-1432.
54. Latham, K. A., K. B. Whittington, R. Zhou, Z. Qian, and E. F. Rosloniec. 2005. Ex vivo characterization of the autoimmune T cell response in the HLA-DR1 mouse model of collagen-induced arthritis reveals long-term activation of type II collagen-specific cells and their presence in arthritic joints. J. Immunol. 174:3978-3985.
55. 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.
56. Legge, K. L., and T. J. Braciale. 2003. Accelerated migration of respiratory dendritic cells to the regional lymph nodes is limited to the early phase of pulmonary infection. Immunity 18:265-277.
57. Lewis, D. B. 2006. Avian flu to human influenza. Annu. Rev. Med. 57:139-154.
58. Lich, J. D., J. A. Jayne, D. Zhou, J. F. Elliott, and J. S. Blum. 2003. Editing of an immunodominant epitope of glutamate decarboxylase by HLA-DM. J. Immunol. 171:853-859.
59. Lopez, C. B., A. Fernandez-Sesma, S. M. Czelusniak, J. L. Schulman, and T. M. Moran. 2000. A mouse model for immunization with ex vivo virus-infected dendritic cells. Cell. Immunol. 206:107-115.
60. Luke, C. J., and K. Subbarao. 2006. Vaccines for pandemic influenza. Emerg. Infect. Dis. 12:66-72.
61. Mallone, R., and G. T. Nepom. 2004. MHC class II tetramers and the pursuit of antigen-specific T cells: define, deviate, delete. Clin. Immunol. 110:232-242.
62. Marsh, S. G. E., P. Parham, and L. D. Barber. 2000. The factsbook series. The HLA factsbook. Academic Press, New York, NY.
63. McHeyzer-Williams, L. J., L. P. Malherbe, and M. G. McHeyzer-Williams. 2006. Helper T cell-regulated B cell immunity. Curr. Top. Microbiol. Immunol. 311:59-83.
64. McHeyzer-Williams, L. J., and M. G. McHeyzer-Williams. 2005. Antigen-specific memory B cell development. Annu. Rev. Immunol. 23:487-513.
65. Mori, M., P. G. Beatty, M. Graves, K. M. Boucher, and E. L. Milford. 1997. HLA gene and haplotype frequencies in the North American population: the National Marrow Donor Program Donor Registry. Transplantation 64:1017-1027.
66. Mustafa, A. S., and F. A. Shaban. 2006. ProPred analysis and experimental evaluation of promiscuous T-cell epitopes of three major secreted antigens of Mycobacterium tuberculosis. Tuberculosis (Edinburgh) 86:115-124.
67. Myers, L. K., Y. Sakurai, E. F. Rosloniec, J. M. Stuart, and A. H. Kang. 2004. An analog peptide that suppresses collagen-induced arthritis. Am. J. Med. Sci. 327:212-216.
68. Myers, L. K., Y. Sakurai, B. Tang, X. He, E. F. Rosloniec, J. M. Stuart, and A. H. Kang. 2002. Peptide-induced suppression of collagen-induced arthritis in HLA-DR1 transgenic mice. Arthritis Rheum. 46:3369-3377.
69. Neumann, G., and Y. Kawaoka. 2006. Host range restriction and pathogenicity in the context of influenza pandemic. Emerg. Infect. Dis. 12:881-886.
70. Northrop, J. K., R. M. Thomas, A. D. Wells, and H. Shen. 2006. Epigenetic remodeling of the IL-2 and IFN-gamma loci in memory CD8 T cells is influenced by CD4 T cells. J. Immunol. 177:1062-1069.
71. + T cells proliferating in response to influenza A antigen. J. Clin. Investig. 104:R63-R67.
72. Pajot, A., M. L. Michel, M. Mancini-Bourgine, M. N. Ungeheuer, D. M. Ojcius, Q. Deng, F. A. Lemonnier, and Y. C. Lone. 2006. Identification of novel HLA-DR1-restricted epitopes from the hepatitis B virus envelope protein in mice expressing HLA-DR1 and vaccinated human subjects. Microbes Infect. 8:2783-2790.
73. Palese, P. 2004. Influenza: old and new threats. Nat. Med. 10:S82-S87.
74. Rammensee, H., J. Bachmann, N. P. Emmerich, O. A. Bachor, and S. Stevanovic. 1999. SYFPEITHI: database for MHC ligands and peptide motifs. Immunogenetics 50:213-219.
75. Reche, P. A., J. P. Glutting, H. Zhang, and E. L. Reinherz. 2004. Enhancement to the RANKPEP resource for the prediction of peptide binding to MHC molecules using profiles. Immunogenetics 56:405-419.
76. Reche, P. A., and E. L. Reinherz. 2005. PEPVAC: a web server for multi-epitope vaccine development based on the prediction of supertypic MHC ligands. Nucleic Acids Res. 33:W138-W42.
77. Reid, A. H., T. G. Fanning, J. V. Hultin, and J. K. Taubenberger. 1999. Origin and evolution of the 1918 "Spanish" influenza virus hemagglutinin gene. Proc. Natl. Acad. Sci. USA 96:1651-1656.
78. 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 (Duluth) 29:282-288.
79. Rojas, J. M., S. E. McArdle, R. B. Horton, M. Bell, S. Mian, G. Li, S. A. Ali, and R. C. Rees. 2005. Peptide immunisation of HLA-DR-transgenic mice permits the identification of a novel HLA-DRbeta1*0101- and HLA-DR-beta1*0401-restricted epitope from p53. Cancer Immunol. Immunother. 54:243-253.
80. Rosloniec, E. F., K. B. Whittington, D. M. Zaller, and A. H. Kang. 2002. HLA-DR1 (DRB1*0101) and DR4 (DRB1*0401) use the same anchor residues for binding an immunodominant peptide derived from human type II collagen. J. Immunol. 168:253-259.
81. Sant, A. J., F. Chaves, S. Jenks, K. Richards, P. Menges, J. M. Weaver, and C. L. Lazarski. 2005. The relationship between immundominance, DM editing, and the kinetic stability of MHC class II:peptide complexes. Immunol. Rev. 207:261-278.
82. Sant, A. J., F. C. Chaves, F. Krafcik, C. A. Lazarski, P. R. Menges, K. A. Richards, and J. Weaver. Immunodominance in CD4 T cell responses: implications for immune responses to influenza virus and for vaccine design. Expert Rev. Vaccines, in press.
83. Schipper, R. F., C. A. van Els, J. D'Amaro, and M. Oudshoorn. 1996. Minimal phenotype panels. A method for achieving maximum population coverage with a minimum of HLA antigens. Hum. Immunol. 51:95-98.
84. Schirle, M., T. Weinschenk, and S. Stevanovic. 2001. Combining computer algorithms with experimental approaches permits the rapid and accurate identification of T cell epitopes from defined antigens. J. Immunol. Methods 257:1-16.
85. Selin, L. K., and R. M. Welsh. 2004. Plasticity of T cell memory responses to viruses. Immunity 20:5-16.
86. Singer, E. 2005. Pandemic fears hatch new methods in flu vaccine industry. Nat. Med. 11:4.
87. Singh, H., and G. P. Raghava. 2001. ProPred: prediction of HLA-DR binding sites. Bioinformatics 17:1236-1237.
88. Sloan, V. S., P. Cameron, G. Porter, M. Gammon, M. Amaya, E. Mellins, and D. M. Zaller. 1995. Mediation by HLA-DM of dissociation of peptides from HLA-DR. Nature 375:802-806.
89. Southwood, S., J. Sidney, A. Kondo, M. F. del Guercio, E. Appella, S. Hoffman, R. T. Kubo, R. W. Chesnut, H. M. Grey, and A. Sette. 1998. Several common HLA-DR types share largely overlapping peptide binding repertoires. J. Immunol. 160:3363-3373.
90. Stephenson, I., K. G. Nicholson, J. M. Wood, M. C. Zambon, and J. M. Katz. 2004. Confronting the avian influenza threat: vaccine development for a potential pandemic. Lancet Infect. Dis. 4:499-509.
91. Stohr, K., and M. Esveld. 2004. Public health. Will vaccines be available for the next influenza pandemic? Science 306:2195-2196.
92. Subbarao, K., B. R. Murphy, and A. S. Fauci. 2006. Development of effective vaccines against pandemic influenza. Immunity 24:5-9.
93. Sun, J. C., and M. J. Bevan. 2003. Defective CD8 T cell memory following acute infection without CD4 T cell help. Science 300:339-342.
94. + T cells after acute infection. Nat. Immunol. 5:927-933.
95. + T cells in protective immunity to influenza. Immunol. Rev. 211:8-22.
96. Tamura, S., and T. Kurata. 2004. Defense mechanisms against influenza virus infection in the respiratory tract mucosa. Jpn. J. Infect. Dis. 57:236-247.
97. Tamura, S., T. Tanimoto, and T. Kurata. 2005. Mechanisms of broad cross-protection provided by influenza virus infection and their application to vaccines. Jpn. J. Infect. Dis. 58:195-207.
98. Teo, S. S., J. S. Nguyen-Van-Tam, and R. Booy. 2005. Influenza burden of illness, diagnosis, treatment, and prevention: what is the evidence in children and where are the gaps? Arch. Dis. Child. 90:532-536.
99. Thomas, P. G., R. Keating, D. J. Hulse-Post, and P. C. Doherty. 2006. Cell-mediated protection in influenza infection. Emerg. Infect. Dis. 12:48-54.
100. 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.
101. 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.
102. van Ham, S. M., U. Gruneberg, G. Malcherek, I. Broker, A. Melms, and J. Trowsdale. 1996. Human histocompatibility leukocyte antigen (HLA)-DM edits peptides presented by HLA-DR according to their ligand binding motifs. J. Exp. Med. 184:2019-2024.
103. Vogt, A. B., S. O. Arndt, G. J. Hammerling, and H. Kropshofer. 1999. Quality control of MHC class II associated peptides by HLA-DM/H2-M. Semin. Immunol. 11:391-403.
104. Vogt, A. B., H. Kropshofer, and G. J. Hammerling. 1997. How HLA-DM affects the peptide repertoire bound to HLA-DR molecules. Hum. Immunol. 54:170-179.
105. Wang, X., and T. Mosmann. 2001. In vivo priming of CD4 T cells that produce interleukin (IL)-2 but not IL-4 or interferon (IFN)-gamma, and can subsequently differentiate into IL-4- or IFN-gamma-secreting cells. J. Exp. Med. 194:1069-1080.
106. Webby, R. J., and R. G. Webster. 2003. Are we ready for pandemic influenza? Science 302:1519-1522.
107. Welsh, R. M., L. K. Selin, and E. Szomolanyi-Tsuda. 2004. Immunological memory to viral infections. Annu. Rev. Immunol. 22:711-743.
108. Wood, J. M. 2002. Selection of influenza vaccine strains and developing pandemic vaccines. Vaccine 20(Suppl. 5):B40-B44.
109. Woodland, D. L., and T. D. Randall. 2004. Anatomical features of anti-viral immunity in the respiratory tract. Semin. Immunol. 16:163-170.
110. Woods, A., H. Y. Chen, M. E. Trumbauer, A. Sirotina, R. Cummings, and D. M. Zaller. 1994. Human major histocompatibility complex class II-restricted T cell responses in transgenic mice. J. Exp. Med. 180:173-181.
111. World Health Organization. 2005. New WHO influenza vaccine recommendations for 2005-2006 season, northern hemisphere. Euro Surveill. 10:E050217.1.
112. Yewdell, J., and A. Garcia-Sastre. 2002. Influenza virus still surprises. Curr. Opin. Microbiol. 5:414-418.
113. Zhao, J., Q. Huang, W. Wang, Y. Zhang, P. Lv, and X. M. Gao. 2007. Identification and characterization of dominant helper T-cell epitopes in the nucleocapsid protein of severe acute respiratory syndrome coronavirus. J. Virol. 81:6079-6088.
114. + T cell memory. J. Immunol. 164:3274-3282.