HLA-A2-binding peptides cross-react not only within the A2 subgroup but also with other HLA-A-Locus allelic products

Tanigaki, Nobuyuki; Fruci, Doriana; Chersi, Alberto; Falasca, Giuliana; Tosi, Roberto; Butler, Richard H.

doi:10.1016/0198-8859(94)90255-0

Cited by 31 publications

(25 citation statements)

References 29 publications

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“…HLA-A2 anchor motifs have been shown to represent a broad cross-reactivity with not only HLA-A2 subgroups but also with A24, A26, and A28. 39,40 Although we did not examine the exact binding affinity of these peptides to HLA molecules, the induction of HM1.24-126-specific CTLs from HLA-A24 ϩ individuals might be explained by this cross-reaction mechanism. In contrast, HM1.24-165 peptide generated specific CTLs mostly from HLA-A24 ϩ individuals, and to a lesser extent from HLA-A2 ϩ individuals.…”

Section: Discussionmentioning

confidence: 99%

Induction of HM1.24 peptide–specific cytotoxic T lymphocytes by using peripheral-blood stem-cell harvests in patients with multiple myeloma

Jalili

Ozaki

Hara

et al. 2005

Blood

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IntroductionMultiple myeloma (MM) is an incurable B-cell malignancy characterized by the accumulation of neoplastic plasma cells mainly in the bone marrow. 1 High-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) as well as molecular-targeting therapy for both MM cells and the bone marrow microenvironment have prolonged overall survival in patients with MM; however, most patients still ultimately have a relapse because of the emergence of residual disease. [2][3][4][5][6] Because cellular immunotherapy, including allogeneic transplantation and donor lymphocyte infusion, is the only approach to induce a cure, [7][8][9] immune-based strategies to eradicate the remaining MM cells have been studied extensively in recent years. 10 Active immunotherapy based on either immunization against tumor-specific antigens or dendritic-cell (DC) vaccines generated ex vivo represents an ideal approach for inducing tumor-specific immunity. 11 Specifically, immunoglobulin idiotype (Id) has been considered as the most specific tumor antigen, and clinical trials using Id-pulsed DC vaccinations have demonstrated cytotoxic T lymphocyte (CTL) responses in some patients with MM. [12][13][14] In addition, generation of MM-specific CTLs has been achieved by using DCs pulsed with MM-cell lysates. 15 Unfortunately, vaccination with Id variations or primary MM-cell lysates cannot provide shared immunotherapy for other MM patients and this problem may limit the wide clinical application of these methods. To date, several tumor-associated antigens such as MUC1, WT-1, Sp-17, NY-ESO-1, SPAN-Xb, and MAGE families have been shown to mediate immune responses against MM cells, 16-21 but these antigens are not consistently expressed on MM cells. 22 Therefore, it is necessary to identify relevant MM-specific antigens for developing more efficient strategies for large numbers of patients with MM.HM1.24 was originally identified as a cell-surface protein that is preferentially overexpressed on MM cells 23 and later was found to be identical to bone marrow stromal cell antigen 2 (BST-2). 24,25 HM1.24/BST-2 (CD317) is also expressed at low levels in selected tissues but is specifically up-regulated in metastatic tumor cells and chemoresistant cancer cells. 26,27 Subsequent studies have revealed that HM1.24 is a type II transmembrane glycoprotein with a unique topology that is present in lipid rafts via a glycosylphosphatidylinositol anchor at the C-terminus and that the rat homologue of cell-surface HM1.24 can be internalized and localized to the trans-Golgi network. 28 Moreover, large-scale analysis of the human cDNA has demonstrated that the HM1.24 gene is one of the important activators of the nuclear factor B pathway that is involved in the pathogenesis of MM. 29 These findings suggest that HM1.24 provides a platform for a signaling complex at the cell 32 Based on these findings, we hypothesized that the generation of HM1.24-specific CTLs might become an attractive strategy for residual disease after PBSCT.In ...

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Section: Discussionmentioning

confidence: 99%

Induction of HM1.24 peptide–specific cytotoxic T lymphocytes by using peripheral-blood stem-cell harvests in patients with multiple myeloma

Jalili

Ozaki

Hara

et al. 2005

Blood

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“…Interestingly, HLA-A2 subgroup molecules were earlier demonstrated to feature high cross-binding propensities to different peptides due to their structural conformity with various residue motifs [31]. Cross-reactivity is a critical phenomenon in cellular immunity where specific MHC epitopes become capable of loading an array of antigenic fragments for the selection and education of T cells for defense against pathogens.…”

Section: Functional Impact Of Hla Class I Genes and Molecules On The mentioning

confidence: 99%

“…In the context of GAD recognition, another indication for the participation of these genes is suggested by the observation that peripheral blood mononuclear cells (PBMC) may respond to GAD peptides with a sequence similar to a protein of Coxsackie B virus. This responsiveness of PBMCs to GAD is certainly not restricted to persons at risk of developing T1DM, but PBMCs of these persons respond significantly more frequently to a sequence encompassing the amino acid residues 247-279 of GAD than healthy persons [30].Since amino acids 247-279 are encoded by a region that has significant sequence similarity to the P2-C protein of Coxsackie B virus, the clinicopathology of T1DM has long been suspected to be due to molecular mimicry, which in turn substantiates the role of MHC class I genes in preclinical stages of T1DM.Interestingly, HLA-A2 subgroup molecules were earlier demonstrated to feature high cross-binding propensities to different peptides due to their structural conformity with various residue motifs [31]. Cross-reactivity is a critical phenomenon in cellular immunity where specific MHC epitopes become capable of loading an array of antigenic fragments for the selection and education of T cells for defense against pathogens.…”

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confidence: 99%

“…In situations where T cells are generated by cross-reactivity of this kind, they become capable of recognizing and reacting even with antigenic peptides other than the original ones that have been used to select these T cells [32]. Indeed peptide cross-binding phenomena were observed for gene products of several MHC class I alleles, such as those of the A2 subgroup and B*2705 [31,33]. Molecular mimicry and T cell cross-reactivity to β-cell autoantigens and environmental agents with sequence similarities are thus proposed mechanisms that may influence the pathogenesis of type 1 diabetes [34,35], but has still not been proven to be causal and the mechanism is criticized because T cells could not be shown to crossreact with GAD in vitro [36].…”

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confidence: 99%

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The Role of HLA Class I Gene Variation in Autoimmune Diabetes

Sia¹,

Weinem²

2005

Rev Diab Stud

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■ AbstractThe use of DNA-based genetic typing has enabled the identification of type 1 diabetes mellitus (T1DM) susceptible and protective major histocompatibility complex (MHC) class II alleles and haplotypes. The application of this approach has also progressed to locate MHC class I alleles that contribute to the clinicopathology of T1DM. Recent studies have shown a widespread involvement of genes from the MHC class I gene region in the clinicopathology of T1DM. These genes are demonstrated to be involved in contributing to progression from the preclinical stage of the disease, which is characterized by the occurrence of islet-specific antibodies, to clinical disease and also to the occurrence of autoimmunity. They can either contribute directly to disease development or indirectly in concert with other susceptible MHC class II alleles or haplotypes via linkage disequilibrium. Class I alleles may also be negatively associated with T1DM. These findings are useful for the development of future strategies in designing tolerogenic approaches for the prevention or even reversal of T1DM. In this article, the latest evidence for the different kinds of participation of HLA class I genes in the etiology of T1DM is reviewed. A metaanalysis which included existing association studies was also carried out in order to re-assess the relevance of class I genes in diabetes development. The analysis of an enlarged heterogeneous sample confirmed the involvement of previously detected serotypes in the etiology of T1DM, such as A24, B8 and B18, and revealed hitherto unknown associations with B60 and B62. The analysis points out that much of the conflicting results of previous association studies originate from inadequate sample sizes and accentuate the value of future investigations of larger samples for identifying linkage in multigenic diseases.Keywords: type 1 diabetes · HLA class I · cross-study analysis · serotype association Introduction ype 1 diabetes mellitus (T1DM) is a multifactorial and multigenic autoimmune organ disease characterized by progressive T cell-mediated destruction of the pancreatic β-cells . The major determinants of this disease are genes of the human leucocyte antigen (HLA) region, which are highly polymorphic. In a multiplicative model, they account for between 20 and 53% of T1DM susceptibility markers [1]. Gene products of HLA class I genes function as antigen presenting molecules for CD8 + cytotoxic T lymphocytes (CTL) and determine the antigen specificity of the CTL-mediated immune response against pathogens and self-antigens. T cell reactions with islet-specific self-antigens may lead to clonal proliferation of autoreactive CTLs directed against pancreatic β-cells provoking destruction of these organ cells.Initial genetic analyses clearly rejected a dominant major locus. In contrast, a series of other genes, such as the coding sequences for TAP (transporters associated with antigen processing), LMP (large multifunc- Copyright © by the SBDR tional proteases) and TNF-α, the MIC-A (MHC class I chain-r...

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“…These patients responded as well as the HLA-A*0201 patients. Subtle differences in the binding and presentation properties of the closely related HLA-A*02 suballeles have been reported (1,3,14). It does not appear, however, that the very similar HLA-A*02 subtypes HLA-A*0201, -A*0202, and -A*0205 behave as functionally distinct HLA allotypes for MV-C 84-92 .…”

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confidence: 99%

Vigorous but Short-Term Gamma Interferon T-Cell Responses against a Dominant HLA-A*02-Restricted Measles Virus Epitope in Patients with Measles

Jaye

Herberts

Jallow

et al. 2003

J Virol

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The absolute and relative abundance of major histocompatibility complex class I-presented viral epitopes is important in the induction and maintenance of antiviral cytotoxic-T-lymphocyte (CTL) responses. We demonstrate that the supra-abundant HLA-A*0201-restricted peptide KLWESPQEI of the measles virus nonstructural C protein induces strong gamma interferon CD8؉ -T-cell responses in children with acute measles. However, longitudinal analysis indicates that these responses are only short-lived. Thus, some viral epitopes that can be immunodominant during primary infection may fail to establish memory CTL responses.

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HLA-A2-binding peptides cross-react not only within the A2 subgroup but also with other HLA-A-Locus allelic products

Cited by 31 publications

References 29 publications

Induction of HM1.24 peptide–specific cytotoxic T lymphocytes by using peripheral-blood stem-cell harvests in patients with multiple myeloma

Induction of HM1.24 peptide–specific cytotoxic T lymphocytes by using peripheral-blood stem-cell harvests in patients with multiple myeloma

The Role of HLA Class I Gene Variation in Autoimmune Diabetes

Vigorous but Short-Term Gamma Interferon T-Cell Responses against a Dominant HLA-A*02-Restricted Measles Virus Epitope in Patients with Measles

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