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 CD8+ Lymphocytes from Simian Immunodeficiency Virus-Infected Rhesus Macaques Recognize 14 Different Epitopes Bound by the Major Histocompatibility Complex Class I Molecule Mamu-A*01: Implications for Vaccine Design and Testing

2001 ◽  
Vol 75 (2) ◽  
pp. 738-749 ◽  
Author(s):  
Todd M. Allen ◽  
Bianca R. Mothé ◽  
John Sidney ◽  
Peicheng Jing ◽  
John L. Dzuris ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Simian Immunodeficiency Virus ◽  
Mhc Class I ◽  
Mononuclear Cells ◽  
Class I ◽  
Binding Motif ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecule ◽  
Immunodeficiency Virus

ABSTRACT It is becoming increasingly clear that any human immunodeficiency virus (HIV) vaccine should induce a strong CD8+ response. Additional desirable elements are multispecificity and a focus on conserved epitopes. The use of multiple conserved epitopes arranged in an artificial gene (or EpiGene) is a potential means to achieve these goals. To test this concept in a relevant disease model we sought to identify multiple simian immunodeficiency virus (SIV)-derived CD8+ epitopes bound by a single nonhuman primate major histocompatibility complex (MHC) class I molecule. We had previously identified the peptide binding motif of Mamu-A*012, a common rhesus macaque MHC class I molecule that presents the immunodominant SIV gag-derived cytotoxic T lymphocyte (CTL) epitope Gag_CM9 (CTPYDINQM). Herein, we scanned SIV proteins for the presence of Mamu-A*01 motifs. The binding capacity of 221 motif-positive peptides was determined using purified Mamu-A*01 molecules. Thirty-seven peptides bound with apparentKd values of 500 nM or lower, with 21 peptides binding better than the Gag_CM9 peptide. Peripheral blood mononuclear cells from SIV-infected Mamu-A*01+ macaques recognized 14 of these peptides in ELISPOT, CTL, or tetramer analyses. This study reveals an unprecedented complexity and diversity of anti-SIV CTL responses. Furthermore, it represents an important step toward the design of a multiepitope vaccine for SIV and HIV.

scholarly journals Major histocompatibility complex class I molecules mediate association of SV40 with caveolae.

1997 ◽  
Vol 8 (1) ◽  
pp. 47-57 ◽  
Author(s):  
E Stang ◽  
J Kartenbeck ◽  
R G Parton
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Mammalian Cells ◽  
Simian Virus 40 ◽  
Class I ◽  
Major Histocompatibility ◽  
Surface Binding ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecule ◽  
Mhc Class I Molecules

Simian virus 40 (SV40) has been shown to enter mammalian cells via uncoated plasma membrane invaginations. Viral particles subsequently appear within the endoplasmic reticulum. In the present study, we have examined the surface binding and internalization of SV40 by immunoelectron microscopy. We show that SV40 associates with surface pits which have the characteristics of caveolae and are labeled with antibodies to the caveolar marker protein, caveolin-1. SV40 is believed to use major histocompatibility complex (MHC) class I molecules as cell surface receptors. Using a number of MHC class I-specific monoclonal antibodies, we found that both viral infection and association of virus with caveolae were strongly reduced by preincubation with anti-MHC class I antibodies. Because binding of SV40 to MHC class I molecules may induce clustering, we investigated whether antibody cross-linked class I molecules also redistributed to caveolae. Clusters of MHC class I molecules were indeed shown to be specifically associated with caveolin-labeled surface pits. Taken together, the results suggest that SV40 may make use of MHC class I molecule clustering and the caveolae pathway to enter mammalian cells.

scholarly journals Impact of Nef-Mediated Downregulation of Major Histocompatibility Complex Class I on Immune Response to Simian Immunodeficiency Virus

2004 ◽  
Vol 78 (23) ◽  
pp. 13335-13344 ◽  
Author(s):  
Tomek Swigut ◽  
Louis Alexander ◽  
Jennifer Morgan ◽  
Jeff Lifson ◽  
Keith G. Mansfield ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Simian Immunodeficiency Virus ◽  
Mhc Class I ◽  
Cellular Response ◽  
Lymphocyte Activation ◽  
Class I ◽  
Wild Type Virus ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus

ABSTRACT Functional activities that have been ascribed to the nef gene product of simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) include CD4 downregulation, major histocompatibility complex (MHC) class I downregulation, downregulation of other plasma membrane proteins, and lymphocyte activation. Monkeys were infected experimentally with SIV containing difficult-to-revert mutations in nef that selectively eliminated MHC downregulation but not these other activities. Monkeys infected with these mutant forms of SIV exhibited higher levels of CD8+ T-cell responses 4 to 16 weeks postinfection than seen in monkeys infected with the parental wild-type virus. Furthermore, unusual compensatory mutations appeared by 16 to 32 weeks postinfection which restored some or all of the MHC-downregulating activity. These results indicate that nef does serve to limit the virus-specific CD8 cellular response of the host and that the ability to downregulate MHC class I contributes importantly to the totality of nef function.

Major Histocompatibility Complex (MHC) Class I Molecule

2016 ◽  
Author(s):  
Douglas M. Templeton ◽  
Michael Schwenk ◽  
Reinhild Klein ◽  
John H. Duffus
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class I ◽  
Class I ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecule

scholarly journals Highly Pathogenic Simian Immunodeficiency Virus mne Variants That Emerge during the Course of Infection Evolve Enhanced Infectivity and the Ability To Downregulate CD4 but Not Class I Major Histocompatibility Complex Antigens

2002 ◽  
Vol 76 (13) ◽  
pp. 6425-6434 ◽  
Author(s):  
Parul G. Patel ◽  
Monica T. Yu Kimata ◽  
Julia E. Biggins ◽  
Joelle M. Wilson ◽  
Jason T. Kimata
Keyword(s):  
Major Histocompatibility Complex ◽  
Simian Immunodeficiency Virus ◽  
Mhc Class I ◽  
Class I ◽  
Major Histocompatibility ◽  
Highly Pathogenic ◽  
Pathogenic Variants ◽  
Histocompatibility Complex ◽  
Immunodeficiency Virus

ABSTRACT The replicative, cytopathic, and antigenic properties of simian immunodeficiency virus (SIV) variants influence its replication efficiency in vivo. To further define the viral properties and determinants that may be important for high-level replication in vivo and progression to AIDS, we compared a minimally pathogenic SIVmne molecular clone with two highly pathogenic variants cloned from late stages of infection. Both variants had evolved greater infectivity than the parental clone due to mutations in nef. Interestingly, a pol determinant in one of the highly pathogenic variants also contributed to its increased infectivity. Furthermore, because replication in vivo may also be influenced by the ability of a virus to evade the cellular immune response of the host, we examined whether the variants were more capable of downregulating surface expression of class I major histocompatibility complex (MHC). Decreased MHC class I expression was not observed in cells infected with any of the viruses. Furthermore, the Nef proteins of the highly pathogenic variants only slightly reduced surface MHC class I expression in transfected cells, although they efficiently downregulated CD4. Together, these data demonstrate that mutations which can enhance viral infectivity, as well as CD4 downregulation, may be important for efficient replication of SIV in the host. However, Nef-mediated reduction of MHC class I expression does not appear to be critical for the increased in vivo replicative ability of highly pathogenic late variants.

scholarly journals 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

2000 ◽  
Vol 74 (16) ◽  
pp. 7400-7410 ◽  
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.

scholarly journals The presentation of a hepatitis C viral peptide by distinct major histocompatibility complex class I allotypes from two chimpanzee species.

1996 ◽  
Vol 183 (2) ◽  
pp. 663-668 ◽  
Author(s):  
S Cooper ◽  
H Kowalski ◽  
A L Erickson ◽  
K Arnett ◽  
A M Little ◽  
...  
Keyword(s):  
Major Histocompatibility Complex ◽  
Hepatitis C ◽  
Mhc Class I ◽  
Pan Paniscus ◽  
Class I ◽  
Major Histocompatibility ◽  
Pygmy Chimpanzee ◽  
Separate Species ◽  
Histocompatibility Complex ◽  
Mhc Class I Molecule

A cytotoxic T lymphocyte (CTL) line, derived from the liver of a common chimpanzee (Pan troglodytes) with hepatitis C, specifically recognized a hepatitis C viral 9-mer peptide (KHP-DATYSR in single-letter amino acid code) bound by the major histocompatibility complex (MHC) class I molecule, Patr-A04. This same CTL line also recognized the identical peptide bound by a structurally different class I molecule, Papa-A06, derived from the separate chimpanzee species, Pan paniscus or pygmy chimpanzee. These class I allotypes differ by six amino acids but, in spite of the structural differences, share the same antigen-presenting function. This is the first observation of antigen presentation to a given T cell receptor by different MHC class I allotypes from separate species.

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