title: MHC-I-restricted epitopes conserved among variola and other related orthopoxviruses are recognized by T cells 30 years after vaccination.
abstract: It is many years since the general population has been vaccinated against smallpox virus. Here, we report that human leukocyte antigen (HLA) class I restricted T cell epitopes can be recognized more than 30 years after vaccination. Using bioinformatic methods, we predicted 177 potential cytotoxic T lymphocyte epitopes. Eight epitopes were confirmed to stimulate IFN-gamma release by T cells in smallpox-vaccinated subjects. The epitopes were restricted by five supertypes (HLA-A1, -A2, -A24 -A26 and -B44). Significant T cell responses were detected against 8 of 45 peptides with an HLA class I affinity of K(D) less than or equal to 5 nM, whereas no T cell responses were detected against 60 peptides with an HLA affinity of K(D) more than 5 nM. All epitopes were fully conserved in seven variola, vaccinia and cowpox strains. Knowledge of the long-term response to smallpox vaccination may lead to a better understanding of poxvirus immunity and may aid in the development of new improved vaccines and diagnostic tools.
authors.affiliation: Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, Lyngby, Denmark.
authors.forename: S T
authors.initials: ST
authors.lastname: Tang
authors.forename: M
authors.initials: M
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Lamberth
authors.forename: M
authors.initials: M
authors.lastname: Harndahl
authors.forename: M H
authors.initials: MH
authors.lastname: Dziegiel
authors.forename: M H
authors.initials: MH
authors.lastname: Claesson
authors.forename: S
authors.initials: S
authors.lastname: Buus
authors.forename: O
authors.initials: O
authors.lastname: Lund
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D018155:Orthopoxvirus / Q000276:immunology*; D012900:Smallpox Vaccine / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D013997:Time Factors
chemical_list: D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D012900:Smallpox Vaccine; D007371:Interferon-gamma
references.citation: J Immunol. 2003 Nov 15;171(10):4969-73
references.pmid: 14607890
references.citation: Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8348-53
references.pmid: 12034885
references.citation: J Immunol. 2005 Feb 15;174(4):2212-9
references.pmid: 15699154
references.citation: J Gen Virol. 2007 Jun;88(Pt 6):1656-1666
references.pmid: 17485524
references.citation: Virology. 1998 Oct 25;250(2):397-407
references.pmid: 9792850
references.citation: Rev Med Virol. 2007 Mar-Apr;17(2):93-113
references.pmid: 17195963
references.citation: Virus Res. 1996 Feb;40(2):169-83
references.pmid: 8725113
references.citation: J Gen Virol. 2005 Nov;86(Pt 11):2925-2936
references.pmid: 16227213
references.citation: Nat Med. 2003 Sep;9(9):1131-7
references.pmid: 12925846
references.citation: Eur J Immunol. 2001 Oct;31(10):2986-96
references.pmid: 11592075
references.citation: Nat Biotechnol. 2006 Jul;24(7):817-9
references.pmid: 16767078
references.citation: Virology. 1996 Jun 1;220(1):10-9
references.pmid: 8659101
references.citation: J Gen Virol. 2002 Aug;83(Pt 8):1965-1976
references.pmid: 12124460
references.citation: Vaccine. 2007 Apr 12;25(15):2823-31
references.pmid: 17254671
references.citation: J Exp Med. 2005 Jan 3;201(1):95-104
references.pmid: 15623576
references.citation: J Gen Virol. 2004 Jan;85(Pt 1):105-117
references.pmid: 14718625
references.citation: Virology. 1990 Nov;179(1):247-66, 517-63
references.pmid: 2219722
references.citation: Virus Res. 1993 Oct;30(1):73-88
references.pmid: 8266721
references.citation: J Virol. 2000 Dec;74(23):11230-9
references.pmid: 11070021
references.citation: J Gen Virol. 2006 Jan;87(Pt 1):29-38
references.pmid: 16361415
references.citation: Immunogenetics. 1999 Nov;50(3-4):201-12
references.pmid: 10602880
references.citation: J Immunol. 2005 Oct 15;175(8):5504-15
references.pmid: 16210659
references.citation: Acta Virol. 1980 Mar;24(2):81-8
references.pmid: 6107030
references.citation: Hum Immunol. 2006 Jul;67(7):512-20
references.pmid: 16829305
references.citation: Vaccine. 2006 Jan 23;24(4):417-25
references.pmid: 16176847
references.citation: Nat Med. 2006 Nov;12(11):1310-5
references.pmid: 17086190
references.citation: Annu Rev Immunol. 1999;17:51-88
references.pmid: 10358753
references.citation: J Immunol. 2007 Jun 1;178(11):6814-20
references.pmid: 17513729
references.citation: J Virol. 2005 Sep;79(18):11724-33
references.pmid: 16140750
references.citation: Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13980-5
references.pmid: 16172378
references.citation: J Virol. 2004 Apr;78(8):3811-6
references.pmid: 15047796
references.citation: Arch Immunol Ther Exp (Warsz). 1999;47(3):135-8
references.pmid: 10470439
references.citation: J Virol. 2004 Jul;78(13):7052-60
references.pmid: 15194781
references.citation: Proc Natl Acad Sci U S A. 2007 Jun 5;104(23):9822-7
references.pmid: 17517620
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):217-22
references.pmid: 12518065
references.citation: J Exp Med. 2003 Apr 7;197(7):927-32
references.pmid: 12668642
references.citation: J Virol. 2001 Apr;75(7):3185-96
references.pmid: 11238845
references.citation: Clin Exp Immunol. 2007 Aug;149(2):265-73
references.pmid: 17488297
references.citation: J Virol. 2006 Jul;80(13):6318-23
references.pmid: 16775319
references.citation: Virology. 1998 May 10;244(2):365-96
references.pmid: 9601507
references.citation: J Infect Dis. 1972 Feb;125(2):161-9
references.pmid: 5007552
references.citation: J Biol Chem. 2004 Aug 27;279(35):36570-8
references.pmid: 15215253
references.citation: Tissue Antigens. 2002 Apr;59(4):251-8
references.pmid: 12135423
references.citation: J Biol Chem. 1995 Jul 7;270(27):15974-8
references.pmid: 7608155
references.citation: Eur J Immunol. 2005 Aug;35(8):2295-303
references.pmid: 15997466
references.citation: J Exp Med. 2004 Jun 7;199(11):1585-93
references.pmid: 15184506
references.citation: Tissue Antigens. 2004 May;63(5):395-400
references.pmid: 15104671
references.citation: Cell. 1995 May 19;81(4):551-60
references.pmid: 7758109
references.citation: Immunogenetics. 2004 Mar;55(12):797-810
references.pmid: 14963618
references.citation: J Mol Biol. 1991 Jun 5;219(3):555-65
references.pmid: 2051488