Identification of the murine H-2Db and human HLA-A*0201 MHC class I-restricted HPV6 E7-specific cytotoxic T lymphocyte epitopes

Peptides presented by major histocompatibility complex (MHC) class I molecules are derived from intracellularly synthesized proteins. Cytosolic proteins are fragmented into peptides, which are subsequently transported via the transporter of antigen presentation (TAP) into the endoplasmic reticulum (ER), where they bind to MHC class I molecules. We have investigated the requirements for MHC class I presentation of the immunodominant gp33 cytotoxic T lymphocyte epitope of the lymphocytic choriomeningitis virus. This epitope is located within the leader peptide of the virus glycoprotein. Such an epitope is expected to be presented in a TAP-independent manner, since it is released into the ER by signal peptidase. Taking advantage of TAP1-/- mice, however, we show both in vitro and in vivo that, after virus infection, the presentation of the gp33 epitope is strictly dependent on a functional TAP heterodimer. The results are discussed with respect to peptide trimming processes in the ER.

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Cross-staining of cytotoxic T lymphocyte populations with peptide-MHC class I multimers of natural HIV-1 variant antigens

AIDS ◽

10.1097/00002030-200101050-00018 ◽

2001 ◽

Vol 15 (1) ◽

pp. 121-122

Author(s):

Annette Oxenius ◽

David A. Price ◽

Sara J. Dawson ◽

Tin Tun ◽

Philippa J. Easterbrook ◽

...

Keyword(s):

Mhc Class I ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Class I ◽

Lymphocyte Populations ◽

Hiv 1

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Escape in One of Two Cytotoxic T-Lymphocyte Epitopes Bound by a High-Frequency Major Histocompatibility Complex Class I Molecule, Mamu-A*02: a Paradigm for Virus Evolution and Persistence?

Journal of Virology ◽

10.1128/jvi.76.22.11623-11636.2002 ◽

2002 ◽

Vol 76 (22) ◽

pp. 11623-11636 ◽

Cited By ~ 69

Author(s):

Thorsten U. Vogel ◽

Thomas C. Friedrich ◽

David H. O'Connor ◽

William Rehrauer ◽

Elizabeth J. Dodds ◽

...

Keyword(s):

Major Histocompatibility Complex ◽

Mhc Class I ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Class I ◽

Major Histocompatibility ◽

Histocompatibility Complex ◽

Mhc Class I Molecule ◽

Immunodeficiency Virus ◽

Ctl Responses

ABSTRACT It is now accepted that an effective vaccine against AIDS must include effective cytotoxic-T-lymphocyte (CTL) responses. The simian immunodeficiency virus (SIV)-infected rhesus macaque is the best available animal model for AIDS, but analysis of macaque CTL responses has hitherto focused mainly on epitopes bound by a single major histocompatibility complex (MHC) class I molecule, Mamu-A*01. The availability of Mamu-A*01-positive macaques for vaccine studies is therefore severely limited. Furthermore, it is becoming clear that different CTL responses are able to control immunodeficiency virus replication with varying success, making it a priority to identify and analyze CTL responses restricted by common MHC class I molecules other than Mamu-A*01. Here we describe two novel epitopes derived from SIV, one from Gag (Gag71-79 GY9), and one from the Nef protein (Nef159-167 YY9). Both epitopes are bound by the common macaque MHC class I molecule, Mamu-A*02. The sequences of these two eptiopes are consistent with the molecule's peptide-binding motif, which we have defined by elution of natural ligands from Mamu-A*02. Strikingly, we found evidence for the selection of escape variant viruses by CTL specific for Nef159-167 YY9 in 6 of 6 Mamu-A*02-positive animals. In contrast, viral sequences encoding the Gag71-79 GY9 epitope remained intact in each animal. This situation is reminiscent of Mamu-A*01-restricted CTL that recognize Tat28-35 SL8, which reproducibly selects for escape variants during acute infection, and Gag181-189 CM9, which does not. Differential selection by CTL may therefore be a paradigm of immunodeficiency virus infection.

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Effects of Retroviral Protease Inhibitors on Proteasome Function and Processing of HIV-Derived MHC Class I-Restricted Cytotoxic T Lymphocyte Epitopes

AIDS Research and Human Retroviruses ◽

10.1089/088922201300343744 ◽

2001 ◽

Vol 17 (11) ◽

pp. 1063-1066 ◽

Cited By ~ 10

Author(s):

Anthony D. Kelleher ◽

Bruce L. Booth ◽

Andrew K. Sewell ◽

Annette Oxenius ◽

Vincenzo Cerundolo ◽

...

Keyword(s):

Protease Inhibitors ◽

Mhc Class I ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Class I ◽

Retroviral Protease

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Definition of Five New Simian Immunodeficiency Virus Cytotoxic T-Lymphocyte Epitopes and Their Restricting Major Histocompatibility Complex Class I Molecules: Evidence for an Influence on Disease Progression

Journal of Virology ◽

10.1128/jvi.74.16.7400-7410.2000 ◽

2000 ◽

Vol 74 (16) ◽

pp. 7400-7410 ◽

Cited By ~ 62

Author(s):

David T. Evans ◽

Peicheng Jing ◽

Todd M. Allen ◽

David H. O'Connor ◽

Helen Horton ◽

...

Keyword(s):

Disease Progression ◽

Mhc Class I ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Rhesus Macaques ◽

Class I ◽

Ctl Epitopes ◽

Histocompatibility Complex ◽

Immunodeficiency Virus ◽

Mhc Class I Molecules

ABSTRACT Simian immunodeficiency virus (SIV) infection of the rhesus macaque is currently the best animal model for AIDS vaccine development. One limitation of this model, however, has been the small number of cytotoxic T-lymphocyte (CTL) epitopes and restricting major histocompatibility complex (MHC) class I molecules available for investigating virus-specific CTL responses. To identify new MHC class I-restricted CTL epitopes, we infected five members of a family of MHC-defined rhesus macaques intravenously with SIV. Five new CTL epitopes bound by four different MHC class I molecules were defined. These included two Env epitopes bound by Mamu-A*11 and -B*03 and three Nef epitopes bound by Mamu-B*03, -B*04, and -B*17. All four restricting MHC class I molecules were encoded on only two haplotypes (b or c). Interestingly, resistance to disease progression within this family appeared to be associated with the inheritance of one or both of these MHC class I haplotypes. Two individuals that inherited haplotypes b and cseparately survived for 299 and 511 days, respectively, while another individual that inherited both haplotypes survived for 889 days. In contrast, two MHC class I-identical individuals that did not inherit either haplotype rapidly progressed to disease (survived <80 days). Since all five offspring were identical at their Mamu-DRBloci, MHC class II differences are unlikely to account for their patterns of disease progression. These results double the number of SIV CTL epitopes defined in rhesus macaques and provide evidence that allelic differences at the MHC class I loci may influence rates of disease progression among AIDS virus-infected individuals.

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A Simian Immunodeficiency Virus Nef Peptide Is a Dominant Cytotoxic T Lymphocyte Epitope in Indian-Origin Rhesus Monkeys Expressing the Common MHC Class I Allele Mamu-A*02

Virology ◽

10.1006/viro.2002.1598 ◽

2002 ◽

Vol 301 (2) ◽

pp. 365-373 ◽

Cited By ~ 16

Author(s):

Michael H. Newberg ◽

Marcelo J. Kuroda ◽

William A. Charini ◽

Ayako Miura ◽

Carol I. Lord ◽

...

Keyword(s):

Simian Immunodeficiency Virus ◽

Mhc Class I ◽

T Lymphocyte ◽

Rhesus Monkeys ◽

Cytotoxic T Lymphocyte ◽

Class I ◽

Indian Origin ◽

Immunodeficiency Virus ◽

The Common

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Mapping and characterization of visna/maedi virus cytotoxic T-lymphocyte epitopes

Journal of General Virology ◽

10.1099/vir.0.2008/002634-0 ◽

2008 ◽

Vol 89 (10) ◽

pp. 2586-2596 ◽

Cited By ~ 3

Author(s):

Changxin Wu ◽

Cyril Barbezange ◽

Ian McConnell ◽

Barbara A. Blacklaws

Keyword(s):

Mhc Class I ◽

T Lymphocyte ◽

Cytotoxic T Lymphocyte ◽

Class I ◽

Virus Infections ◽

Recombinant Vaccinia ◽

Modified Vaccinia Virus Ankara ◽

Immunodeficiency Virus ◽

Vaccinia Viruses

CD8+ cytotoxic T-lymphocyte (CTL) responses have been shown to be important in the control of human and simian immunodeficiency virus infections. Infection of sheep with visna/maedi virus (VISNA), a related lentivirus, induces specific CD8+ CTL in vivo, but the specific viral proteins recognized are not known. To determine which VISNA antigens were recognized by sheep CTL, we used recombinant vaccinia viruses expressing the different genes of VISNA: in six sheep (Finnish Landrace×Dorset crosses, Friesland and Lleyn breeds) all VISNA proteins were recognized except TAT. Two sheep, shown to share major histocompatibility complex (MHC) class I alleles, recognized POL and were used to map the epitope. The pol gene is 3267 bp long encoding 1088 aa. By using recombinant vaccinia viruses a central portion (nt 1609–2176, aa 537–725) was found to contain the CTL epitope and this was mapped with synthetic peptides to a 25 aa region (aa 612–636). When smaller peptides were used, a cluster of epitopes was detected: at least three epitopes were present, at positions 612–623: DSRYAFEFMIRN; 620–631: MIRNWDEEVIKN; and 625–635: EEVIKNPIQAR. A DNA-prime-modified vaccinia virus Ankara (MVA)-boost strategy was employed to immunize four sheep shown to share MHC class I allele(s) with the sheep above. Specific CTL activity developed in all the immunized sheep within 3 weeks of the final MVA boost although half the sheep showed evidence of specific reactivity after the DNA-prime immunizations. This is the first report, to our knowledge, of induction of CTL by a DNA-prime-boost method in VISNA infection.

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