Autoreactivity against induced or upregulated abundant self-peptides in HLA-A*0201 following measles virus infection

Herberts, Carla; Brink, Jacqueline van Gaans‐van den; Heeft, E.d van der; Wijk, Margot van; Hoekman, Jan; Jaye, Assan; Poelen, Martien C. M.; Boog, Claire J. P.; Roholl, P. J. M.; Whittle, Hilton; Jong, Annemieke de; Els, Cecile van

doi:10.1016/s0198-8859(02)00707-3

Cited by 37 publications

(43 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, it was not significantly up-regulated, confirming earlier reports on the variedly increased expression of this epitope after MV infection (37 The values represent the copy numbers of the peptides on the infected cells and on the non-infected cells (in parentheses). …”

Section: Table Isupporting

confidence: 87%

Stable Isotope Tagging of Epitopes

Meiring

Soethout²,

Poelen³

et al. 2006

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

Identification of peptides presented in major histocompatibility complex (MHC) class I molecules after viral infection is of strategic importance for vaccine development. Until recently, mass spectrometric identification of virus-induced peptides was based on comparative analysis of peptide pools isolated from uninfected and virusinfected cells. Here we report on a powerful strategy aiming at the rapid, unambiguous identification of naturally processed MHC class I-associated peptides, which are induced by viral infection. The methodology, stable isotope tagging of epitopes (SITE), is based on metabolic labeling of endogenously synthesized proteins during infection. This is accomplished by culturing virus-infected cells with stable isotope-labeled amino acids that are expected to be anchor residues (i. The adaptive immune response to virus infections is characterized by the generation of CD8 ϩ cytotoxic T lymphocytes (CTLs), 1 which recognize peptides presented by MHC class I molecules of infected cells. The MHC class I molecules display peptides from proteins expressed inside the cell that are usually generated in the classical proteasomal pathway. Under physiological conditions these peptides are derived from self-proteins. During viral infection, the MHC class I display of peptides is affected due to changes in host protein expression and as a result of the production of viral proteins (1, 2). Identification and quantification of such altered MHC-peptide expression is a goal as part of a new field of research referred to as immunoproteomics and is of strategic importance for vaccine development (1, 3-5). The analytical challenge lies in the discrimination between the few disease-related peptides among a majority of nondisease-related peptides (6). Several strategies have been developed to explore changes in the MHC-associated peptide display on antigen-presenting cells. These analyses are generally based on the isolation of the MHC-peptide complexes, acid elution of the bound peptides from the MHC molecules followed by analysis using LC and MS as pioneered by Hunt et al. (7) and adapted for various purposes by other groups (4, 8 -11). We successfully used the mass spectrometric method to identify novel MHC class I-restricted viral epitopes by subtractive analysis of peptide pools isolated from virus-infected and control cells (9). This comparative method, however, needs meticulous parallel sample processing of the infected and control peptide batches, and differences in peptide recovery as well as chromatographic retention and stability between uninfected and infected peptide samples cannot be excluded. This has limited the use of subtractive analysis and might have led to the failure to identify viral epitopes (8, 10).The importance of CD8 ϩ T cells in the recovery from respiratory infections such as measles virus (MV) or respiratory syncytial virus (RSV) is generally acknowledged (12,13

show abstract

Section: Table Isupporting

confidence: 87%

Stable Isotope Tagging of Epitopes

Meiring

Soethout²,

Poelen³

et al. 2006

Molecular & Cellular Proteomics

View full text Add to dashboard Cite

show abstract

“…Indeed, this mechanism is supported by a recent study demonstrating autoreactivity following measles virus-induced up-regulation of self peptides (17). Irrespective of possible function, these host-derived peptide ligands provide an expanded view of peptide presentation to the immune system following viral infection.…”

Section: Peptide Changes Occur Early In Infectionmentioning

confidence: 82%

Cutting Edge: Class I Presentation of Host Peptides Following HIV Infection

Hickman

Luis

Bardet

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

Class I MHC molecules bind intracellular peptides for presentation to cytotoxic T lymphocytes. Identification of peptides presented by class I molecules during infection is therefore a priority for detecting and targeting intracellular pathogens. To understand which host-encoded peptides distinguish HIV-infected cells, we have developed a mass spectrometric approach to characterize HLA-B*0702 peptides unique to or up-regulated on infected T cells. In this study, we identify 15 host proteins that are differentially presented on infected human T cells. Peptides with increased expression on HIV-infected cells were derived from multiple categories of cellular proteins including RNA binding proteins and cell cycle regulatory proteins. Therefore, comprehensive analysis of the B*0702 peptide repertoire demonstrates that marked differences in host protein presentation occur after HIV infection.

show abstract

“…enhanced display of self-peptides in MHC class I, which led to the temporary activation of autoreactive T cells and autoimmunity (38).…”

Section: Discussionmentioning

confidence: 99%

IFNβ Accelerates Autoimmune Type 1 Diabetes in Nonobese Diabetic Mice and Breaks the Tolerance to β Cells in Nondiabetes-Prone Mice

Alba

Puertas

Carrillo

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

Genetic and environmental factors are decisive in the etiology of type 1 diabetes. Viruses have been proposed as a triggering environmental event and some evidences have been reported: type I IFNs exist in the pancreata of diabetic patients and transgenic mice expressing these cytokines in β cells develop diabetes. To determine the role of IFNβ in diabetes, we studied transgenic mice expressing human IFNβ in the β cells. Autoimmune features were found: MHC class I islet hyperexpression, T and B cells infiltrating the islets and transfer of the disease by lymphocytes. Moreover, the expression of β2-microglobulin, preproinsulin, and glucagon in the thymus was not altered by IFNβ, thus suggesting that the disease is caused by a local effect of IFNβ, strong enough to break the peripheral tolerance to β cells. This is the first report of the generation of NOD (a model of spontaneous autoimmune diabetes) and nonobese-resistant (its homologous resistant) transgenic mice expressing a type I IFN in the islets: transgenic NOD and nonobese-resistant mice developed accelerated autoimmune diabetes with a high incidence of the disease. These results indicate that the antiviral cytokine IFNβ breaks peripheral tolerance to β cells, influences the insulitis progression and contributes to autoimmunity in diabetes and nondiabetes- prone mice.

show abstract

Autoreactivity against induced or upregulated abundant self-peptides in HLA-A*0201 following measles virus infection

Cited by 37 publications

References 48 publications

Stable Isotope Tagging of Epitopes

Stable Isotope Tagging of Epitopes

Cutting Edge: Class I Presentation of Host Peptides Following HIV Infection

IFNβ Accelerates Autoimmune Type 1 Diabetes in Nonobese Diabetic Mice and Breaks the Tolerance to β Cells in Nondiabetes-Prone Mice

Contact Info

Product

Resources

About