scholarly journals Murine cytotoxic T lymphocyte recognition of individual influenza virus proteins. High frequency of nonresponder MHC class I alleles.

1988 ◽  
Vol 168 (5) ◽  
pp. 1935-1939 ◽  
Author(s):  
J R Bennink ◽  
J W Yewdell
Keyword(s):  
Influenza Virus ◽  
Mhc Class I ◽  
Cytotoxic T Lymphocyte ◽  
Critical Factor ◽  
Class I ◽  
Foreign Protein ◽  
Outbred Populations ◽  
High Degree ◽  
Ctl Responses ◽  
Virus Proteins

We determined the MHC restriction of CTL responses to five individual influenza virus proteins. Four viral proteins failed to be recognized in conjunction with three of the five class I alleles of the H-2k and H-2d haplotypes, while the fifth was recognized only in conjunction with a single allele. This indicates that there is a significant chance that a given class I allele will be associated with low responsiveness or nonresponsiveness for a given foreign protein. This explains, at least in part, why MHC-linked nonresponsiveness is frequently detected in polyclonal antiviral CTL responses. Most importantly, these findings support the idea that responsiveness to foreign antigens is a critical factor in maintaining the high degree of MHC class I polymorphism in outbred populations.

scholarly journals 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?

2002 ◽  
Vol 76 (22) ◽  
pp. 11623-11636 ◽  
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.

scholarly journals HLA-B57-Restricted Cytotoxic T-Lymphocyte Activity in a Single Infected Subject toward Two Optimal Epitopes, One of Which Is Entirely Contained within the Other

2000 ◽  
Vol 74 (11) ◽  
pp. 5291-5299 ◽  
Author(s):  
Philip J. R. Goulder ◽  
Yanhua Tang ◽  
Stephen I. Pelton ◽  
Bruce D. Walker
Keyword(s):  
Mhc Class I ◽  
Cytotoxic T Lymphocyte ◽  
Hla Class I ◽  
Class I ◽  
Peptide Epitopes ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus ◽  
Lymphocyte Activity ◽  
Ctl Responses

ABSTRACT Viral peptides are recognized by cytotoxic T lymphocytes (CTL) as a complex with major histocompatibility complex (MHC) class I molecules, but the extent to which a single HLA allele can accommodate epitope peptides of different length and sequence is not well characterized. Here we report the identification of clonal CTL responses from the same donor that independently recognize one of two HLA-B57-restricted epitopes, KAFSPEVIPMF (KF11; p24Gag residues 30 to 40) and KAFSPEVI (KF8; p24Gag residues 30 to 37). Although lysis studies indicated that the KF11 peptide stabilized the HLA-B57-peptide complex more efficiently than the KI8 peptide, strong clonal responses were directed at each epitope. In samples from a second donor, the same phenomenon was observed, in which distinct CTL clones recognized peptide epitopes presented by the same HLA class I allele (in this case, HLA-A3) which were entirely overlapping. These data are relevant to the accurate characterization of CTL responses, which is fundamental to a detailed understanding of MHC class I-restricted immunity. In addition, these studies demonstrate marked differences in the length of peptides presented by HLA-B57, an allele which is associated with nonprogressive human immunodeficiency virus infection.

scholarly journals Vaccine-Elicited Memory Cytotoxic T Lymphocytes Contribute to Mamu-A*01-Associated Control of Simian/Human Immunodeficiency Virus 89.6P Replication in Rhesus Monkeys

2005 ◽  
Vol 79 (8) ◽  
pp. 4580-4588 ◽  
Author(s):  
Michael S. Seaman ◽  
Sampa Santra ◽  
Michael H. Newberg ◽  
Valerie Philippon ◽  
Kelledy Manson ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Mhc Class I ◽  
T Lymphocyte ◽  
Rhesus Monkeys ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
Immunodeficiency Virus ◽  
Memory Cytotoxic T Lymphocytes ◽  
The Impact ◽  
Ctl Responses

ABSTRACT The expression of particular major histocompatibility complex (MHC) class I alleles can influence the rate of disease progression following lentiviral infections. This effect is a presumed consequence of potent cytotoxic T-lymphocyte (CTL) responses that are restricted by these MHC class I molecules. The present studies have examined the impact of the MHC class I allele Mamu-A*01 on simian/human immunodeficiency virus 89.6P (SHIV-89.6P) infection in unvaccinated and vaccinated rhesus monkeys by exploring the contribution of dominant-epitope specific CTL in this setting. Expression of Mamu-A*01 in immunologically naive monkeys was not associated with improved control of viral replication, CD4+ T-lymphocyte loss, or survival. In contrast, Mamu-A*01 + monkeys that had received heterologous prime/boost immunizations prior to challenge maintained higher CD4+ T-lymphocyte levels and better control of SHIV-89.6P replication than Mamu-A*01 − monkeys. This protection was associated with the evolution of high-frequency anamnestic CTL responses specific for a dominant Mamu-A*01-restricted Gag epitope following infection. These data indicate that specific MHC class I alleles can confer protection in the setting of a pathogenic SHIV infection by their ability to elicit memory CTL following vaccination.

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

2016 ◽  
Vol 65 (3) ◽  
pp. 261-271 ◽  
Author(s):  
Shiwen Peng ◽  
Austin Mattox ◽  
Simon R. Best ◽  
Anca M. Barbu ◽  
James A. Burns ◽  
...  
Keyword(s):  
Mhc Class I ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Class I

scholarly journals Relevance of viral context and diversity of antigen-processing routes for respiratory syncytial virus cytotoxic T-lymphocyte epitopes

2008 ◽  
Vol 89 (9) ◽  
pp. 2194-2203 ◽  
Author(s):  
Carolina Johnstone ◽  
Sara Guil ◽  
Miguel A. Rico ◽  
Blanca García-Barreno ◽  
Daniel López ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Mhc Class I ◽  
Antigen Processing ◽  
Cytotoxic T Lymphocyte ◽  
Class I ◽  
F Protein ◽  
Mhc Class I Molecule ◽  
Presentation Pathway ◽  
Syncytial Virus ◽  
In Cells

Antigen processing of respiratory syncytial virus (RSV) fusion (F) protein epitopes F85–93 and F249–258 presented to cytotoxic T-lymphocytes (CTLs) by the murine major histocompatibility complex (MHC) class I molecule Kd was studied in different viral contexts. Epitope F85–93 was presented through a classical endogenous pathway dependent on the transporters associated with antigen processing (TAP) when the F protein was expressed from either RSV or recombinant vaccinia virus (rVACV). At least in cells infected with rVACV encoding either natural or cytosolic F protein, the proteasome was required for epitope processing. In cells infected with rVACV encoding the natural F protein, an additional endogenous TAP-independent presentation pathway was found for F85–93. In contrast, epitope F249–258 was presented only through TAP-independent pathways, but presentation was brefeldin A sensitive when the F protein was expressed from RSV, or mostly resistant when expressed from rVACV. Therefore, antigen-processing pathways with different mechanisms and subcellular localizations are accessible to individual epitopes presented by the same MHC class I molecule and processed from the same protein but in different viral contexts. This underscores both the diversity of pathways available and the influence of virus infection on presentation of epitopes to CTLs.

scholarly journals Strictly transporter of antigen presentation (TAP)-dependent presentation of an immunodominant cytotoxic T lymphocyte epitope in the signal sequence of a virus protein.

1995 ◽  
Vol 182 (5) ◽  
pp. 1615-1619 ◽  
Author(s):  
J Hombach ◽  
H Pircher ◽  
S Tonegawa ◽  
R M Zinkernagel
Keyword(s):  
Antigen Presentation ◽  
Mhc Class I ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Signal Sequence ◽  
Class I ◽  
Signal Peptidase ◽  
Leader Peptide ◽  
Virus Protein ◽  
Mhc Class I Molecules

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.

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

AIDS ◽  
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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