Influence of HLA-DR1 β chain positions 85 and 86 on binding and conformation of DR1-restricted antigenic peptides

Newton-Nash, Debra K.; Eckels, David D.

doi:10.1016/0198-8859(92)90150-l

Cited by 20 publications

(26 citation statements)

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“…HeLa cells transfected with the MHC CIITA (HeLa CIITA) express the product of the homozygous DRB*0102 allele and bind more efficiently a HA 307-318 peptide variant with a tyrosine-to-leucine substitution at position 3 (HA-PKL) (22,23). As expected, in the absence of DMY, binding of HA-PKL was slightly more efficient than HA-PKY on HeLa CIITA (Fig.…”

Section: Dmy Increases Peptide Loadingsupporting

confidence: 64%

Forced Expression of HLA-DM at the Surface of Dendritic Cells Increases Loading of Synthetic Peptides on MHC Class II Molecules and Modulates T Cell Responses

Pezeshki

Côté

Azar

et al. 2011

The Journal of Immunology

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Adoptive transfer of autologous dendritic cells (DCs) loaded with tumor-associated CD4 and CD8 T cell epitopes represents a promising avenue for the immunotherapy of cancer. In an effort to increase the loading of therapeutic synthetic peptides on MHC II molecules, we used a mutant of HLA-DM (DMY) devoid of its lysosomal sorting motif and that accumulates at the cell surface. Transfection of DMY into HLA-DR+ cells resulted in increased loading of the exogenously supplied HA307–318 peptide, as well as increased stimulation of HA-specific T cells. Also, on transduction in mouse and human DCs, DMY increased loading of HEL48–61 and of the tumor Ag-derived gp100174–190 peptides, respectively. Interestingly, expression of DMY at the surface of APCs favored Th1 differentiation over Th2. Finally, we found that DMY− and DMY+ mouse APCs differentially stimulated T cell hybridomas sensitive to the fine conformation of peptide–MHC II complexes. Taken together, our results suggest that the overexpression of HLA-DMY at the plasma membrane of DCs may improve quantitatively, but also qualitatively, the presentation of CD4 T cell epitopes in cellular vaccine therapies for cancer.

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Section: Dmy Increases Peptide Loadingsupporting

confidence: 64%

Forced Expression of HLA-DM at the Surface of Dendritic Cells Increases Loading of Synthetic Peptides on MHC Class II Molecules and Modulates T Cell Responses

Pezeshki

Côté

Azar

et al. 2011

The Journal of Immunology

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show abstract

“…This position is occupied by either a glycine for alleles 101, 401, 701, and 1101 or a valine for the alleles 301, 1301, and 1501. This dimorphism valine/glycine is known to control the P1 anchor residue (11,28,32,38) and to contribute to the dimer stability of HLA II molecules (39). Our binding data suggest that position ␤86 segregates the preponderant alleles upon different binding modes.…”

Section: Discussionmentioning

confidence: 64%

HLA-DR Restricted Peptide Candidates for Bee Venom Immunotherapy

Texier

Pouvelle

Busson

et al. 2000

The Journal of Immunology

125

155

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T cell epitopes containing peptides have been recently proposed as an alternative to conventional immunotherapy of allergic diseases because they are expected to be better tolerated than allergen extracts. A principal limitation to their clinical use is that they present an important diversity, which primarily results from the polymorphism of HLA class II molecules. In Caucasian populations, however, seven alleles of the most expressed molecules (namely DRB1*0101, DRB1*0301, DRB1*0401, DRB1*0701, DRB1*1101, DRB1*1301, and DRB1*1501) predominate. Peptides from allergens that would efficiently bind to them should be potential candidates for specific immunotherapy. In this paper, we have determined the peptides present in the major bee venom allergen by investigating the capacity of synthetic peptides that encompass its whole sequence to bind to each allele. Several efficient binders have been identified and are either allele-specific or common to several HLA-DR molecules. Interestingly enough, the 81–97 sequence is universal in the sense that it binds to all studied molecules. This sequence is surrounded by several active regions, which make the 76–106 sequence particularly rich of binding determinants and a good candidate for specific immunotherapy. Statistical analyses of the binding data also provide an overview of the preponderant HLA-DR alleles specificity.

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“…DRB1*0102 differs from DRB1*0101 by only 2 amino acids. Although both changes are in the peptidebinding groove, DRB1*0101 and *0102 have been shown in some cases to present the same peptides for T cell recognition; in other cases, it has been shown that peptide presentation differs between the 2 alleles [56,57]. Nonetheless, an extended DRB1*01 supermotif for class II molecules may well exist between closely related alleles such as DRB1*0101 and DRB1*0102.…”

Section: Discussionmentioning

confidence: 99%

Influence of HLA Supertypes on Susceptibility and Resistance to Human Immunodeficiency Virus Type 1 Infection

et al. 2000

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Certain human leukocyte antigens, by presenting conserved immunogenic epitopes for T cell recognition, may, in part, account for the observed differences in human immunodeficiency virus type 1 (HIV-1) susceptibility. To determine whether HLA polymorphism influences HIV-1 susceptibility, a longitudinal cohort of highly HIV-1-exposed female sex workers based in Nairobi, Kenya, was prospectively analyzed. Decreased HIV-1 infection risk was strongly associated with possession of a cluster of closely related HLA alleles (A2/6802 supertype; incidence rate ratio [IRR], 0.45; 95% confidence interval [CI], 0.27-0.72; P=.0003). The alleles in this supertype are known in some cases to present the same peptide epitopes for T cell recognition. In addition, resistance to HIV-1 infection was independently associated with HLA DRB1*01 (IRR, 0.22; 95% CI, 0.06-0.60; P=.0003), which suggests that anti-HIV-1 class II restricted CD4 effector mechanisms may play an important role in protecting against viral challenge. These data provide further evidence that resistance to HIV-1 infection in this cohort of sex workers is immunologically mediated.

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Influence of HLA-DR1 β chain positions 85 and 86 on binding and conformation of DR1-restricted antigenic peptides

Cited by 20 publications

References 0 publications

Forced Expression of HLA-DM at the Surface of Dendritic Cells Increases Loading of Synthetic Peptides on MHC Class II Molecules and Modulates T Cell Responses

Forced Expression of HLA-DM at the Surface of Dendritic Cells Increases Loading of Synthetic Peptides on MHC Class II Molecules and Modulates T Cell Responses

HLA-DR Restricted Peptide Candidates for Bee Venom Immunotherapy

Influence of HLA Supertypes on Susceptibility and Resistance to Human Immunodeficiency Virus Type 1 Infection

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