Single amino acid substitutions on a Japanese cedar pollen allergen (Cry j 1)-derived peptide induced alterations in human T cell responses and T cell receptor antagonism

Ikagawa, Shuji; Matsushita, Sho; Chen, Yu Zhen; Ishikawa, Takeru; Nishimura, Yasuharu

doi:10.1016/s0091-6749(96)70283-x

Cited by 81 publications

(43 citation statements)

References 37 publications

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“…P1 and P4 appear to be the major determinants of specific peptide binding. Some previous mutagenesis studies of DR52c-binding peptides support this view (16,22); for example, in the CRj 1 peptide, the substitution of a P1 Leu to Ser completely abrogates binding to DR52c, and mutation of the P4 Asn to Ala or Gln also inhibits binding (16). Particularly revealing are studies of the Ras peptide.…”

Section: Resultsmentioning

confidence: 90%

“…The P6 and P9 pockets are more tolerant of different residues; for example, changing the P6 Arg to Ser in the p53 (243-253) peptide does not inhibit binding to DR52c (22), and likewise, substitution of Gly to Ser or Ala in P6 or of Thr to Ala or Ser in P9 of the CRj 1 peptide does not impair DR52c's ability to activate T cells (16). Interestingly, from the structure, we can see how an Arg or Lys, such as found in the p53 peptide or one of the tetanus peptides shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Although the DRB3 gene-encoded molecules have not been as well studied as those encoded by DRB1 genes, these MHCII molecules have been linked to several autoimmune diseases; for example, DR52a has been associated with Crohn's sarcoidosis (8), Graves' disease (9,10), and Löfgren's syndrome (11); DR52b has been associated with Graves' disease (12), multiple sclerosis (13), and essential hypertension caused by Chlamydia pneumoniae infection (14); and DR52c has been related to Crohn's disease (15) and cedar pollen allergies (16). Recently, we identified DR52c as the MHC-restriction element for a human nickel-reactive T cell isolated from a patient with contact sensitivity to nickel in jewelry (4).…”

mentioning

confidence: 99%

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The structure of HLA-DR52c: Comparison to other HLA-DRB3 alleles

Dai

Crawford

Marrack

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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Class II major histocompatibility complex (MHCII) molecules present antigens to CD4 ؉ T cells. In addition to the most commonly studied human MHCII isotype, HLA-DR, whose ␤ chain is encoded by the HLA-DRB1 locus, several other isotypes that use the same ␣ chain but have ␤ chains encoded by other genes. These other DR molecules also are expressed in antigen-presenting cells and are known to participate in peptide presentation to T cells and to be recognized as alloantigens by other T cells. Like some of the HLA-DRB1 alleles, several of these alternate DR molecules have been associated with specific autoimmune diseases and T cell hypersensitivity. Here we present the structure of an HLA-DR molecule (DR52c) containing one of these alternate ␤ chains (HLA-DRB3*0301) bound to a self-peptide derived from the Tu elongation factor. The molecule shares structurally conserved elements with other MHC class II molecules but has some unique features in the peptide-binding groove. Comparison of the three major HLA-DBR3 alleles (DR52a, b, and c) suggests that they were derived from one another by recombination events that scrambled the four major peptide-binding pockets at peptide positions 1, 4, 6, and 9 but left virtually no polymorphisms elsewhere in the molecules.antigen presentation ͉ MHC Class II ͉ peptide antigens ͉ peptide motif ͉ x-ray structure

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Section: Resultsmentioning

confidence: 90%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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The structure of HLA-DR52c: Comparison to other HLA-DRB3 alleles

Dai

Crawford

Marrack

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…The peptide M12p54 -68 (NRDLEQAYNELSGEA) and a T cell clone, YN5-32, were prepared as previously described (21)(22)(23). In brief, the CD4 ϩ ␣␤ T cell clone YN5-32 restricted by HLA-DR4 (DRA*0101 ϩ DRB1*0406) was established by stimulating PBMC with soluble M12p54 -68 peptide as previously described (21).…”

Section: Peptides and T Cell Clonementioning

confidence: 99%

An Amiloride-Sensitive and Voltage-Dependent Na+ Channel in an HLA-DR-Restricted Human T Cell Clone

Lai

Chen

Nishimura

et al. 2000

The Journal of Immunology

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We investigated changes in voltage-gated Na+ currents and effects of extracellular Na+ on proliferation in HLA-DR-restricted human CD4+ αβ T cells after stimulation with a non-self antigenic peptide, M12p54–68. In the absence of antigenic peptide, neither single (n = 80) nor APC-contacted (n = 71) T cells showed voltage-gated inward currents recording with whole-cell patch-clamp techniques, even with Ca2+ and Na+ ions present in the perfusion solution. However, with the same recording conditions, 31% (26 of 84) of APC-contacted T cells stimulated with the antigenic peptide showed voltage-dependent inward currents that were elicited from −60 mV. The inward currents were not inhibited in extracellular Ca2+-free conditions or in the presence of 1 mM NiCl2. However, they were completely inhibited in extracellular Na+-free conditions, which were made by replacing Na+ with iso-osmotic N-methyl-d-glucamine or choline. The Na+ currents were insensitive to tetrodotoxin, a classical blocker of Na+ channels, but were dose-dependently inhibited by amiloride, a potassium-sparing pyrazine diuretic. Furthermore, the Ag-specific proliferative response of T cells was completely inhibited in Na+-free Tyrode’s solution and was suppressed by amiloride in a dose-dependent manner. Our findings suggest that activation of amiloride-sensitive and voltage-gated Na+ channels would be an important step to allow an adequate influx of Na+ and maintain a sustained high Ca2+ level during T cell activation.

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“…Antigen-specific proliferation of the T cell clone was investigated, as described [25]. L cell transfectants were used as APC, and peptide pulse of L cell transfectants was done as follows: L cell transfectants were treated with 20 g/ml of mitomycin C (SIGMA) as described [26], and 3.5 ϫ 10 4 cells/well were incubated with Dulbecco's Modified Eagle Medium supplemented with 10% fetal calf serum and the indicated peptide in a 96-well plate for 16 h, followed by two washings with RPMI 1640.…”

Section: T Cell Proliferation Assaymentioning

confidence: 99%

The CLIP-substituted invariant chain efficiently targets an antigenic peptide to HLA class II pathway in L cells

et al. 1998

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ABSTRACT:The presentation of antigenic peptides by major histocompatibility complex (MHC) class II to CD4 ϩ T cells is crucial to initiate immune responses. We developed a new system for delivery of an antigenic peptide to the MHC class II pathway, using the invariant chain (Ii). We designed a mutated human p33-form Ii, CLIP-substituted Ii, in which streptococcal M12p55-68 (RDLEQAYNELSGEA) was substituted for CLIP (class II associated invariant chain peptide) . We examined the peptide presenting function of this construct, in comparison with the previously reported C-terminal fused Ii, in which a cathepsin cleavage site and M12p54-68 was ligated to the C-terminus of Ii. Mouse L cell transfectants expressing either of these two mutated Ii along with HLA-DR4 could process and present M12p55-68 to the peptide specific and DR4-restricted CD4 ϩ T cell clone. CLIP-substituted Ii was much more efficient in antigen presentation than was the C-terminal fused Ii. Similar to the wild-type Ii, the CLIP-substituted Ii was associated intracellularly with DR4 molecules. These results indicate that the peptide substituted for CLIP of Ii p33 bound to the groove of DR molecules in the same manner as CLIP and it was preferentially presented to the CD4 ϩ T cell clone in the absence of HLA-DM molecules. This system may prove useful for immunotherapy with DNA vaccines or for construction of an antigen presenting cell library with diverse peptides.

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Single amino acid substitutions on a Japanese cedar pollen allergen (Cry j 1)-derived peptide induced alterations in human T cell responses and T cell receptor antagonism

Cited by 81 publications

References 37 publications

The structure of HLA-DR52c: Comparison to other HLA-DRB3 alleles

The structure of HLA-DR52c: Comparison to other HLA-DRB3 alleles

An Amiloride-Sensitive and Voltage-Dependent Na+ Channel in an HLA-DR-Restricted Human T Cell Clone

The CLIP-substituted invariant chain efficiently targets an antigenic peptide to HLA class II pathway in L cells

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