The MHC Genes

Rammensee, Hans‐Georg; Bachmann, Jutta; Stevanović, Stefan

doi:10.1007/978-3-662-22162-4_2

Cited by 15 publications

(29 citation statements)

References 766 publications

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“…Currently, 1245 MHC I alleles are known in the human species (http://www3.ebi.ac.uk/ services/imgt/hla/cgi-bin/statistics.cgi). Polymorphic variations are mainly restricted to amino acid substitutions in the peptide-binding groove (6,7). As a result, each MHC I molecule binds a distinct set of peptides.…”

Section: The Pmhc I Complexmentioning

confidence: 99%

“…The consensus motifs of the set of peptides bound by each MHC I molecule were first identified by sequencing the mixture of peptides eluted from MHC I molecules (4,8). In a comprehensive list compiled by Rammensee and his colleagues (6), there are 48 distinct sequence motifs for 69 MHC I molecules. Thus, the antigen-processing machinery operating with essentially conserved components is nevertheless capable of generating highly diverse sets of peptides that satisfy the binding preferences of a large number of different MHC I molecules.…”

Section: The Pmhc I Complexmentioning

confidence: 99%

“…Experimentally, it is possible to generate pMHC I complexes by expressing minigenes that encode only the minimal antigenic peptide (9,10). However, in natural protein precursors, the antigenic peptides are located in the internal positions with both N-and C-terminal flanking residues (6). Thus, beginning with a large protein, proteolytic processes must remove all N-and C-terminal flanking residues to generate the final peptide.…”

Section: The Pmhc I Complexmentioning

confidence: 99%

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All the peptides that fit: the beginning, the middle, and the end of the MHC class I antigen‐processing pathway

Shastri

Cardinaud

Schwab

et al. 2005

Immunological Reviews

120

101

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The end result of the antigen-processing pathway is the display of peptide-bound major histocompatibility complex I (pMHC I) molecules. The pMHC I molecules are expressed on the cell surface where they can be surveyed by CD8(+) T cells for abnormal proteins. MHC I molecules present a large repertoire of peptides that fit perfectly in their binding grooves and represent the otherwise hidden intracellular contents. Many peptides originate as defective ribosomal products in the cytoplasm. In a stepwise manner, the antigen-processing pathway generates and protects the proteolytic intermediates until they yield the final peptides that can fit the MHC I in the endoplasmic reticulum.

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Section: The Pmhc I Complexmentioning

confidence: 99%

Section: The Pmhc I Complexmentioning

confidence: 99%

Section: The Pmhc I Complexmentioning

confidence: 99%

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All the peptides that fit: the beginning, the middle, and the end of the MHC class I antigen‐processing pathway

Shastri

Cardinaud

Schwab

et al. 2005

Immunological Reviews

120

101

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“…The algorithm (www.syfpeithi.de) was used for prediction of binding to HLA-A*0201 of 5T4 9mer peptides. 24…”

Section: Mass Spectrometrymentioning

confidence: 99%

“…The activation of specific T cells is initiated by professional antigen presenting cells, which optimally integrate the antigen processing and MHC-peptide complex presentation and provide the obligate costimulatory signals necessary for differentiation and expansion of T cells. 21 Potential CTL epitopes can be identified by computer-based prediction [22][23][24] and in vitro sensitization of CTLs against these putative peptides. Testing the recognition pattern of the generated T cells toward cells that endogenously express the antigen can confirm their relevance.…”

mentioning

confidence: 99%

Cd8 T‐cell recognition of human 5T4 oncofetal antigen

Smyth

Elkord

Taher

et al. 2006

Intl Journal of Cancer

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The 5T4 oncofetal antigen is expressed by a wide variety of human carcinomas, including colorectal, ovarian and gastric carcinomas. The restricted expression of 5T4 on tumor tissues as well as its implication in tumor progression and bad prognosis makes 5T4 a promising new candidate for immunotherapy. An MVA vaccine encoding 5T4 antigen has been successfully evaluated in preclinical studies in a murine tumor model. Here, we report the generation of human CD8 T cells specific for the 5T4 antigen by stimulation with autologous monocyte derived DC infected with a replication defective adenovirus encoding the 5T4 cDNA (Ad5T4). Analysis of several donors confirms a repertoire of such CD8 responses. In a parallel approach, incorporating the results of proteasome-mediated digestion of 5T4 derived 35-mer peptides and the potential high affinity epitopes predicted by a computer-based algorithm, we identified 8 putative HLA-A*0201-presented CD8 MHC class I epitopes of 5T4 antigen. Two of these generated specific CD8 T cells after restimulation with peptide loaded autologous DC and assay by cytotoxicity and IFNc ELISPOT. Moreover these particular peptide generated T cells recognized naturally 5T4 positive tumor cells only if they expressed HLA-A*0201 as judged by IFNc ELISPOT or ELISA. Also, HLA-A*0201 CD8 T cells recognized these peptides in a DC-Ad5T4 polyclonal response. In conclusion, there is a repertoire of CD8 T cell recognition of 5T4 in normal human donors and some candidate HLA-A*0201 epitopes have been identified. ' 2006 Wiley-Liss, Inc.Key words: 5T4 oncofetal antigen; dendritic cells; adenovirus; proteasome; CD8 T cells There are several types of human tumor-associated antigens (TAAs), which are being exploited as targets for developing immunotherapies against malignant tumors. 1-4 Such antigens include, over or selectively expressed normal molecules (differentiation, oncofetal antigens), viral-and tumor-specific antigens, including mutated products (sometimes functional in the transformed state). Human 5T4 is a 72 kDa cell surface oncofetal antigen defined by a monoclonal antibody raised against wheat germ agglutinin-glycoproteins isolated from human syncytiotrophoblast microvillus plasma membranes. 5,6 The 5T4 antigen is highly expressed in trophoblast, but shows relatively limited expression in other normal tissues. 7 In contrast, the 5T4 antigen is upregulated in a wide variety of human carcinomas, including colorectal, gastric and ovarian carcinomas, where it is associated with poor clinical outcome. [8][9][10][11][12] The restricted expression of 5T4 antigen on tumor tissues as well as its association with tumor progression makes it a promising new candidate for immunotherapy. Several approaches to developing immunotherapies against this target are under development. Thus, we are harnessing the tumor cell surface expression of 5T4, by using antibodies to targeted drugs and/ or activation of effectors 13,14 or retargeting using chimeric immune receptors of polyclonal T-cell populations. 15,16 Our work in...

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Know thy immune self and non‐self: Proteomics informs on the expanse of self and non‐self, and how and where they arise

Joyce

Ternette

2021

Proteomics

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T cells play an important role in the adaptive immune response to a variety of infections and cancers. Initiation of a T cell mediated immune response requires antigen recognition in a process termed MHC (Major Histocompatibility Complex) restriction. A T cell antigen is a composite structure made up of a peptide fragment bound within the antigen-binding groove of an MHC-encoded class I or class II molecule. Insight into the precise composition and biology of self and non-self immunopeptidomes is essential to harness T cell mediated immunity to prevent, treat, or cure infectious diseases and cancers. T cell antigen discovery is an arduous task! The pioneering work in the early 1990s has made large-scale T cell antigen discovery possible. Thus, advancements in mass spectrometry coupled with proteomics and genomics technologies make possible T cell antigen discovery with ease, accuracy, and sensitivity. Yet we have only begun to understand the breadth and the depth of self and non-self immunopeptidomes because the molecular biology of the cell continues to surprise us with new secrets directly related to the source, and the processing and presentation of MHC ligands. Focused on MHC class I molecules, this review, therefore, provides a brief historic account of T cell antigen discovery and, against a backdrop of key advances in molecular cell biologic processes, elaborates on how proteogenomics approaches have revolutionized the field.

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The MHC Genes

Cited by 15 publications

References 766 publications

All the peptides that fit: the beginning, the middle, and the end of the MHC class I antigen‐processing pathway

All the peptides that fit: the beginning, the middle, and the end of the MHC class I antigen‐processing pathway

Cd8 T‐cell recognition of human 5T4 oncofetal antigen

Know thy immune self and non‐self: Proteomics informs on the expanse of self and non‐self, and how and where they arise

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