Noncanonical peptides in complex with MHC class I

Apostolopoulos, Vasso; Lazoura, Eliada

doi:10.1586/14760584.3.2.151

Cited by 16 publications

(18 citation statements)

References 28 publications

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“…Cw4, HLA-E, and HLA-G are represented by 1MI9, 1MEH, and 1YDP, respectively. Apostolopoulos and Lazoura, 2004). Some of these cases might also be due to binding mechanisms that involve coupled variation of the anchor residues.…”

Section: Discussionmentioning

confidence: 99%

Structures of an MHC Class I Molecule from B21 Chickens Illustrate Promiscuous Peptide Binding

et al. 2007

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Little is known about the structure of major histocompatibility complex (MHC) molecules outside of mammals. Only one class I molecule in the chicken MHC is highly expressed, leading to strong genetic associations with infectious pathogens. Here, we report two structures of the MHC class I molecule BF2*2101 from the B21 haplotype, which is known to confer resistance to Marek's disease caused by an oncogenic herpesvirus. The binding groove has an unusually large central cavity, which confers substantial conformational flexibility to the crucial residue Arg9, allowing remodeling of key peptide-binding sites. The coupled variation of anchor residues from the peptide, utilizing a charge-transfer system unprecedented in MHC molecules, allows peptides with conspicuously different sequences to be bound. This promiscuous binding extends our understanding of ways in which MHC class I molecules can present peptides to the immune system and might explain the resistance of the B21 haplotype to Marek's disease.

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Section: Discussionmentioning

confidence: 99%

Structures of an MHC Class I Molecule from B21 Chickens Illustrate Promiscuous Peptide Binding

et al. 2007

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“…A variety of strategies have been developed to enhance DNA vaccine efficacy. These approaches include: (1) modification of DNA vaccines to include improved expression plasmids 1 or incorporation of viral vectors 2 ; (2) modifications of cDNA sequences encoding antigen to enhance antigenicity, 3 codon adjustments to optimize transcription, 1,4 or generation of string-ofepitope constructs incorporating selected subunits of antigens 5,6 ; (3) improved delivery systems, including methods for more efficient in vivo transfection of host cells, such as in vivo electroporation 6 or gene gun 7 ; and (4) the use of adjuvants. 8 Adjuvants include conventional adjuvants, such as Freund adjuvant, and the more recently developed chemically defined ("molecular") adjuvants.…”

Section: Introductionmentioning

confidence: 99%

Enhancement of DNA tumor vaccine efficacy by gene gun–mediated codelivery of threshold amounts of plasmid-encoded helper antigen

Leitner

Baker

Berenberg

et al. 2009

Blood

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Nucleic acid-based vaccines are effective in infectious disease models but have yielded disappointing results in tumor models when tumor-associated selfantigens are used. Incorporation of helper epitopes from foreign antigens into tumor vaccines might enhance the immunogenicity of DNA vaccines without increasing toxicity. However, generation of fusion constructs encoding both tumor and helper antigens may be difficult, and resulting proteins have unpredictable physical and immunologic properties. Furthermore, simultaneous production of equal amounts of highly immunogenic helper and weakly immunogenic tumor antigens in situ could favor development of responses against the helper antigen rather than the antigen of interest. We assessed the ability of 2 helper antigens (␤-galactosidase or fragment C of tetanus toxin) encoded by one plasmid to augment responses to a self-antigen (lymphomaassociated T-cell receptor) encoded by a separate plasmid after codelivery into skin by gene gun. This approach allowed ad- IntroductionPlasmid-encoded antigens have been used to induce immune responses in experimental animals and humans for more than a decade. Plasmid-based nucleic acid vaccines are attractive because of simplicity, low cost, and safety, but suboptimal immunogenicity and limited efficacy against certain pathogens and tumors have limited their utility. A variety of strategies have been developed to enhance DNA vaccine efficacy. These approaches include:(1) modification of DNA vaccines to include improved expression plasmids 1 or incorporation of viral vectors 2 ; (2) modifications of cDNA sequences encoding antigen to enhance antigenicity, 3 codon adjustments to optimize transcription, 1,4 or generation of string-ofepitope constructs incorporating selected subunits of antigens 5,6 ; (3) improved delivery systems, including methods for more efficient in vivo transfection of host cells, such as in vivo electroporation 6 or gene gun 7 ; and (4) the use of adjuvants. 8 Adjuvants include conventional adjuvants, such as Freund adjuvant, and the more recently developed chemically defined ("molecular") adjuvants. The latter are intended to enhance immune responses while avoiding, or at least significantly reducing, adverse effects associated with conventional adjuvants.Entities with a wide variety of biologic effects have been used as chemically defined adjuvants for DNA vaccines, including biologic response modifiers such as cytokines (eg, granulocytemacrophage colony-stimulating factor [GM-CSF] 9 ) and costimulatory molecules 10,11 as well as monoclonal antibodies (mAbs) that block undesired or trigger desired pathways, such as anti-CD40 12 or anti-CD137. 13 An alternative strategy involves codelivery of "helper antigens" (ie, foreign antigens that induce strong T-cell responses) with weak antigens of interest. Helper antigens are selected based on their high immunogenicity and enhance responses to weaker antigens via incompletely characterized bystander effects. Proteins previously used as helper antigens include keyh...

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“…Although it is clear that so-called primary anchors do often dominate binding, we have shown unequivocally [108], as have others [168], that binding motifs, as descriptions of the process, are fundamentally flawed. Not hopeless, not useless, but partial and incomplete.…”

Section: Discussionmentioning

confidence: 48%

Computational Chemistry, Informatics, and the Discovery of Vaccines

Guan¹,

Davies²,

Taylor³

et al. 2005

CAD

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Perhaps the most exciting sub-discipline within Bioinformatics is the application of informatic methods to immunology. Immunoinformatics, which combines informatics with computational chemistry, is facilitating important change within immunology. As it frees itself from the empirical straight jacket that has characterised its development, immunoinformatics is helping immunology to engage fully with the dynamic post-genomic revolution sweeping through bioscience. Focussing on quantitative aspects, we will review recent developments within immunoinformatics, paying particular attention to the following: the development of functional immunological databases; prediction of the antigen presentation pathway; predicting the specificity of peptide Major Histocompatibility Complex (MHC) interactions, using statistical techniques and atomistic molecular dynamics; and the grouping of MHC molecules into supertypes.

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Noncanonical peptides in complex with MHC class I

Cited by 16 publications

References 28 publications

Structures of an MHC Class I Molecule from B21 Chickens Illustrate Promiscuous Peptide Binding

Structures of an MHC Class I Molecule from B21 Chickens Illustrate Promiscuous Peptide Binding

Enhancement of DNA tumor vaccine efficacy by gene gun–mediated codelivery of threshold amounts of plasmid-encoded helper antigen

Computational Chemistry, Informatics, and the Discovery of Vaccines

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