Assembly of MHC class I molecules analyzed in vitro

Townsend, Alain; Elliott, Tim; Cerundolo, Vincenzo; Foster, L.; Barber, Brian H.; Tse, A. G. D.

doi:10.1016/0092-8674(90)90366-m

Cited by 471 publications

(282 citation statements)

References 44 publications

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“…Alternatively, CPV could prevent the exit of peptide-loaded MHC I molecules, a mechanism used by viral "anti-chaperones" (15). The binding of high affinity peptides to MHC I results in a complex that is more stable than "empty" MHC I heterodimers (31). To determine whether CPV infections cause a defect in the peptide loading of MHC class I molecules, we therefore determined the thermostability of MHC I molecules in the lysates of CPV-infected HeLa cells.…”

Section: Cpv Infection Does Not Affect the Thermostability Of Mhc Imentioning

confidence: 99%

Cowpox Virus Evades CTL Recognition and Inhibits the Intracellular Transport of MHC Class I Molecules

Dasgupta

Hammarlund

Slifka

et al. 2007

The Journal of Immunology

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Orthopoxviruses evade host immune responses by using a number of strategies, including decoy chemokine receptors, regulation of apoptosis, and evasion of complement-mediated lysis. Different from other poxviral subfamilies, however, orthopoxviruses are not known to evade recognition by CTL. In fact, vaccinia virus (VV) is used as a vaccine against smallpox and a vector for eliciting strong T cell responses to foreign Ags. and both human and mouse T cells are readily stimulated by VV-infected APC in vitro. Surprisingly, however, CD8+ T cells of mice infected with cowpox virus (CPV) or VV recognized APC infected with VV but not APC infected with CPV. Likewise, CD8+ T cells from vaccinated human subjects could not be activated by CPV-infected targets and CPV prevented the recognition of VV-infected APC upon coinfection. Because CD8+ T cells recognize viral peptides presented by MHC class I (MHC I), we examined surface expression, total levels, and intracellular maturation of MHC I in CPV- and VV-infected human and mouse cells. Although total levels of MHC I were unchanged, CPV reduced surface levels and inhibited the intracellular transport of MHC I early during infection. CPV did not prevent peptide loading of MHC I but completely inhibited MHC I exit from the endoplasmic reticulum. Because this inhibition was independent of viral replication, we conclude that an early gene product of CPV abrogates MHC I trafficking, thus rendering CPV-infected cells “invisible” to T cells. The absence of this immune evasion mechanism in VV likely limits virulence without compromising immunogenicity.

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Section: Cpv Infection Does Not Affect the Thermostability Of Mhc Imentioning

confidence: 99%

Cowpox Virus Evades CTL Recognition and Inhibits the Intracellular Transport of MHC Class I Molecules

Dasgupta

Hammarlund

Slifka

et al. 2007

The Journal of Immunology

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“…Indeed, Boyd et al showed that the number of high affinity binding sites increased when p^rn was used together with purified soluble analogues of MHC molecules [36]. Second, p^m may selectively bind to the heavy chain which is already stabilized by a binding peptide [37]. Finally, Otten et al reported that when the fern-heavy chain complex begins to dissociate it would become more accessible to peptide binding [38].…”

Section: Effect Of Human Iv-mmentioning

confidence: 99%

Identification of peptide sequences that potentially trigger HLA‐A2.1‐restricted cytotoxic T lymphocytes

Nijman¹,

Houbiers²,

Vierboom³

et al. 1993

Eur J Immunol

181

142

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We used the human processing defective cell line 174CEM.T2 (T2) to identify potential cytotoxic T lymphocyte (CTL) epitopes of human proteins. Exogenously added peptides can increase the number of properly folded HLA‐A2.1 molecules on the cell surface of T2 cells, as shown by immunofluorescence measurements using the mouse monoclonal antibody BB7.2 (anti‐HLA‐A2.1) and fluorescein isothiocyanate‐labeled goat anti‐mouse F(ab')2 antibody. The peptides were selected on the basis of a computer score derived from the recently described HLA‐A2.1 specific motif. Analysis of the influenza matrix protein showed that 15 out of 35 high‐scoring peptides up‐regulate the expression of HLA‐A2.1 molecules on theT2 cell surface. The combination of the computer scoring program and an immunofluorescence‐based peptide binding assay allows rapid detection of potential CTL target peptides.

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“…Transport of class I molecules to the cell surface is dependent on their binding to antigenic peptides generated in the lumen of the endoplasmic reticulum (ER) (Townsend et al, 1990). These peptides, which arise from proteolytic cleavage in the cytosol, are delivered to the ER by the action of a protein complex referred to as the transporter associated with antigen processing or TAP (reviewed by Elliott, 1997).…”

mentioning

confidence: 99%

Transcriptional regulation of the major histocompatibility complex (MHC) class I heavy chain, TAP1 and LMP2 genes by the human papillomavirus (HPV) type 6b, 16 and 18 E7 oncoproteins

2000

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We have examined the possibility that the E7 proteins of the high-risk human papillomavirus (HPV) type 16 and 18 and the oncogenic adenovirus (Ad) type 12 E1A protein share the ability to down-regulate the expression of components of the antigen processing and presentation pathway, as a common strategy in the evasion of immune surveillance during the induction of cell transformation. Expression of the HPV 18 E7 oncoprotein, like Ad 12 E1A, resulted in repression of the major histocompatibility complex (MHC) class I heavy chain promoter, as well as repression of a bidirectional promoter that regulates expression of the genes encoding the transporter associated with antigen processing subunit 1 (TAP1) and a proteasome subunit, low molecular weight protein 2 (LMP2). HPV 16 E7 also caused a reduction in class I heavy chain promoter activity, however it did not have any signi®cant e ect on the activity of the bidirectional promoter. Interestingly, expression of the low-risk HPV 6b E7 protein resulted in an increase in MHC class I heavy chain promoter activity, while repressing the TAP1/LMP2 promoter. Interference with the class I pathway could also explain the ability of low-risk HPVs in inducing benign lesions. Oncogene (2000) 19, 4930 ± 4935.

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Assembly of MHC class I molecules analyzed in vitro

Cited by 471 publications

References 44 publications

Cowpox Virus Evades CTL Recognition and Inhibits the Intracellular Transport of MHC Class I Molecules

Cowpox Virus Evades CTL Recognition and Inhibits the Intracellular Transport of MHC Class I Molecules

Identification of peptide sequences that potentially trigger HLA‐A2.1‐restricted cytotoxic T lymphocytes

Transcriptional regulation of the major histocompatibility complex (MHC) class I heavy chain, TAP1 and LMP2 genes by the human papillomavirus (HPV) type 6b, 16 and 18 E7 oncoproteins

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