A promiscuous T cell hybridoma restricted to various I‐A molecules

Katoh, Masahito; Itoh, Yasushi; Ogasawara, Kunio; Kajino, Kiichi; Nishihori, H.; Takahashi, Akio; Matsuki, Naoto; Iwabuchi, Kazuya; Yoshida, Takato O.; Good, Robert A.; Onoé, Kazunori

doi:10.1002/eji.1830260503

Cited by 4 publications

(2 citation statements)

References 28 publications

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“…This model served also as explanation for promiscuous recognition of peptides by H-2 I-E-restricted murine clones (15). Recent publications, however, describe recognition of one peptide presented by H-2 I-A molecules which display polymorphism in both the α and β chain (16)(17)(18)(19).…”

Section: Discussionmentioning

confidence: 99%

Allele-unrestricted presentation of lidocaine by HLA-DR molecules to specific alphabeta+ T cell clones

Zanni¹

1998

International Immunology

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T cells recognize peptide and non-peptide antigens. Drugs represent typical examples of non-peptide antigens. The majority of drug-specific T cells are alphabeta+ TCR T cells and are MHC class I or II restricted. Here we show the existence of drug (lidocaine)-specific T cell clones which proliferate in the presence of antigen-presenting cells (APC) with different HLA alleles. Two clones (SFT24 and E20) were analyzed in detail. They show a narrow dose-dependent proliferation to lidocaine, but not to procaine. With the use of a panel of HLA-typed allogeneic APC, we observed that certain allogeneic APC plus lidocaine lead to a similar, others to partial and some to no proliferation of the lidocaine-specific T cell clones. An APC-independent proliferation could be excluded since both clones proliferated only marginally without APC and increasing the number of APC resulted in a higher proliferation. Blocking experiments with anti-DP, -DQ and -DR antibodies showed that lidocaine is presented in a HLA-DR-restricted way both with autologous or allogeneic APC. Mouse fibroblasts transfected with an allogeneic HLA-DRB1*01 but not HLA-DR-negative mouse fibroblasts could serve as presenting cells. Fixation of APC did not hamper drug presentation, but pulsing of APC with the drug was not possible, indicating that processing is not required and that lidocaine binds in an unstable way to the MHC-peptide complex. This degenerate drug recognition has certain features of superantigen recognition, such as the ability of drugs to bind from the outside to multiple HLA-DR alleles. Such features of drug recognition may open new therapeutic possibilities to intervene with TCR-MHC interactions in a selective way.

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Section: Discussionmentioning

confidence: 99%

Allele-unrestricted presentation of lidocaine by HLA-DR molecules to specific alphabeta+ T cell clones

Zanni¹

1998

International Immunology

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“…Such a vaccine could have a high level of flexibility if conserved sequences were coupled to other protective B-or T-cell epitopes and if it had the capacity to generate protective T-cell responses in a genetically diverse population. A subset of promiscuous peptides that are recognized in the context of multiple murine or human class II alleles has been described (10,13,18,19,27,28,32,33,43,44,60). Degenerate binding of peptides to multiple alleles of murine I-E, and its human homolog HLA-DR, has been attributed to the presence of a monomorphic ␣ chain.…”

Section: Discussionmentioning

confidence: 99%

Identification of an I-E^d-Restricted T-Cell Epitope ofEscherichia coliOuter Membrane Protein F

Williams

Bigley

2004

Infect Immun

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A predominant T-cell epitope ofat either the C or the N terminus of the sequence was used, the minimal epitope was determined. Critical residues were determined by using alanine-substituted peptide analogues. T-cell hybridomas were only stimulated by peptides that encompassed amino acids 295 to 303 (9-mer), and the core sequence required a minimum of three additional amino acids at either the amino or the carboxy terminus to induce IL-2 secretion. Critical residues were determined to be phenylalanine at position 295, threonine at position 300, and tyrosines at positions 301 and 302. This study is the first to identify a minimal T-cell epitope and major histocompatibility complex restriction element of the OmpF protein and confirms previous observations that there is considerable degeneracy in the length of peptides that can bind I-E d and variability in the amino acid composition of the C and N termini of these peptides. Antigen recognition by CD4ϩ T cells involves the uptake and proteolysis of native proteins by antigen-presenting cells, followed by the association and surface presentation of smaller peptide fragments bound to class II major histocompatibility complex (MHC) molecules. Interaction of this complex with clonotypic receptors on the surface of T cells results in a cascade of intracellular events collectively termed T-cell activation. Acid elution, followed by protein sequencing of naturally processed peptides from affinity-purified human and murine class II molecules (13,14,17,29,41,47,64,65), has shown considerable variability in the length of bound peptides (11 to 17 amino acids in length) and that a single determinant may be presented as multiple peptide species, depending on the length of the amino-or carboxy-terminal flanking residues. Crystallographic analysis of the MHC class II molecule HLA-DR1 (9, 62) provided the structural explanation for the heterogeneity in length of class II-bound peptides since it was observed that peptides are bound in an extended conformation inside the binding groove, which is open at both ends, unlike the class I peptide-binding groove. Additionally, binding studies have revealed that peptide anchor residues (or their respective binding sites within the groove) are more degenerate in their specificity compared to the stringent binding of class I ligands. While allele-specific binding motifs for class II molecules have been more difficult to identify because of the open-ended structure of the peptide-binding groove and the resulting heterogeneity of bound peptides, several allele-specific motifs have emerged (http://syfpeithi.bmi-heidelberg.com/).Porins are a family of heterotrimeric pore-forming molecules present in the outer membranes of gram-negative members of the family Enterobacteriaceae. Monomeric porin molecules associate to form stable trimeric hydrophilic transmembrane channels that allow passive diffusion of solutes, including antibiotics, across the lipid bilayer. The primary amino acid sequence of porins from several species of the family Enterobacteri...

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Development of peptide vaccines inducing production of neutralizing antibodies against HIV-1 viruses in HLA-DQ6 mice

Takahashi

Ogasawara

Matsuki

et al. 1998

Vaccine

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A promiscuous T cell hybridoma restricted to various I‐A molecules

Cited by 4 publications

References 28 publications

Allele-unrestricted presentation of lidocaine by HLA-DR molecules to specific alphabeta+ T cell clones

Allele-unrestricted presentation of lidocaine by HLA-DR molecules to specific alphabeta+ T cell clones

Identification of an I-E^d-Restricted T-Cell Epitope ofEscherichia coliOuter Membrane Protein F

Development of peptide vaccines inducing production of neutralizing antibodies against HIV-1 viruses in HLA-DQ6 mice

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A promiscuous T cell hybridoma restricted to various I‐A molecules

Cited by 4 publications

References 28 publications

Allele-unrestricted presentation of lidocaine by HLA-DR molecules to specific alphabeta+ T cell clones

Allele-unrestricted presentation of lidocaine by HLA-DR molecules to specific alphabeta+ T cell clones

Identification of an I-Ed-Restricted T-Cell Epitope ofEscherichia coliOuter Membrane Protein F

Development of peptide vaccines inducing production of neutralizing antibodies against HIV-1 viruses in HLA-DQ6 mice

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Identification of an I-E^d-Restricted T-Cell Epitope ofEscherichia coliOuter Membrane Protein F