Potential therapeutic recombinant proteins comprised of peptides containing recombined T cell epitopes

Rogers, Bruce L.; Bond, Julian F.; Craig, Sandra J.; Nault, Anneliese K.; Segal, Debra B.; Morgenstern, Jay P.; Meei-Song, Chen; Bizinkauskas, Christine B.; Counsell, Catherine M.; Lussier, Annette M.; Luby, Thomas M.; Kuo, Mei-Chang; Briner, Thomas J.; Garman, Richard D.

doi:10.1016/0161-5890(94)90090-6

Cited by 32 publications

(12 citation statements)

References 33 publications

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“…Desensitization therapy with Fel d 1 peptides [22] was reportedly successful, using two peptides that stimulate T cells o f a majority of patients allergic to Fel d 1. From a similar standpoint, the combination ofDerfl p 18-31 + Der f 1 p206-223 or Der f 1 p75-94 + Der f 1 p206-223 stimulat ed T cells of all 6 subjects listed in figure 1.…”

Section: Antigen-presenting Hla Moleculesmentioning

confidence: 99%

<i>Dermatophagoides farinae</i>-1-Derived Peptides and HLA Molecules Recognized by T Cells from Atopic Individuals

Matsuoka

Kohrogi²,

Ando³

et al. 1997

Int Arch Allergy Immunol

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Der f 1, the group I allergen in Dermatophagoides farinae extracts, is a major source of inhalation allergens in Japan. Using the mixture of a panel of overlapping synthetic peptides that spread over the entire Der f 1 molecule, we found that polyclonal Der f 1-specific short-term T cell lines prepared from peripheral blood of 6 individuals allergic to Der f who carry most of the common HLA haplotypes seen in the Japanese population can respond to 16 different peptides. Eight of 16 peptides stimulated T cells of more than 2 donors, regardless of the HLA types. Proliferative responses of four T cell lines were markedly inhibited by mAb HU4 (anti-HLA-DRB1+B5), one was inhibited partially by HU11 (anti-HLA-DQ4+5+6), and one was inhibited fully by a combination of HU4, L243 (anti-HLA-DRB1+B4) and PLM16 (anti-HLA-DRB3) but only partially by each of these mAbs. One of these T cell lines, DT, of which the proliferative response was partially inhibited by HUH, was cloned. Indeed, the T cell clones were restricted by DQ6 molecules on an HLA-DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 haplotype. These results indicate that patients’ T cells recognize Der f 1 in association mainly with HLA-DRA/DRB1, but that DQA1/DQB1, DRA/DRB3 and possibly DRA/DRB4 gene products also function as antigen-presenting molecules. Thus, although some peptides have a more potent T cell-stimulatory activity than others, the T cell receptor ligands formed with the Der f 1 molecule are highly heterogeneous.

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Section: Antigen-presenting Hla Moleculesmentioning

confidence: 99%

<i>Dermatophagoides farinae</i>-1-Derived Peptides and HLA Molecules Recognized by T Cells from Atopic Individuals

Matsuoka

Kohrogi²,

Ando³

et al. 1997

Int Arch Allergy Immunol

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“…Even though the functional elimination of allergen-specific T cells is the primary aim of this approach, a beneficial decrease of IgE-mediated reactions is also achieved [16,17]. One possibility could be the use of recombinant constructs that contain non-contiguous T-cellreactive areas [18] or epitope-rich regions of allergenic molecules [19]. In addition, the individual variation of T-cell recognition of epitopes further complicates the situation [4].…”

Section: Discussionmentioning

confidence: 99%

Mutant derivatives of the main respiratory allergen of cow are less allergenic than the intact molecule

Kauppinen

Zeiler²,

Rautiainen³

et al. 1999

Clin Experimental Allergy

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“…Peptide vaccines have several advantages: a defined chemical structure, simplicity of preparation, and prolonged shelf life. They also appear to be safe because, at least in mice, T-cell peptides do not bind to IgE [51]; however, human immune responses to allergens are more complex than murine immune responses. Various theoretical constraints are predictable: (1) some major allergens, particularly pollen allergens, contain several T-cell epitopes that are recognized by allergic individuals; (2) certain major allergens appear to have various isoforms containing cross-reacting and non-cross-reacting epitopes, which increase the repertoire of allergenic epitopes [52]; (3) allergic individuals differ with respect to their recognition of these epitopes; (4) B-cell and T-cell epitopes may be present on the same peptide, which increases the risk of systemic reactions; and (5) excessive doses of some peptides may induce autoimmune reactions.…”

Section: Experimental It Approachesmentioning

confidence: 99%

Immunotherapy for allergies and asthma: present and future

Mohapatra

Qazi

Hellermann

2010

Current Opinion in Pharmacology

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Allergen immunotherapy (IT) is a proven approach for treating allergic rhinitis and allergic asthma that has been practiced since 1911 and has undergone significant development in the last two decades. As currently practiced, IT involves subcutaneous or sublingual administration of allergens, both methods of which have been extensively investigated. In addition to allergen IT, a number of additional nonspecific IT approaches are being used or are in phase II/phase III clinical trials, which may be available in clinics within the next one to three years. Such therapies include anti-IgE antibodies and the soluble IL-4 receptor. Other experimental IT approaches are at the preclinical research stage and may proceed to clinical trials and the clinic within the next five to ten years. This review discusses the pros and cons of recent developments in both currently practiced and experimental IT approaches.

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Potential therapeutic recombinant proteins comprised of peptides containing recombined T cell epitopes

Cited by 32 publications

References 33 publications

<i>Dermatophagoides farinae</i>-1-Derived Peptides and HLA Molecules Recognized by T Cells from Atopic Individuals

<i>Dermatophagoides farinae</i>-1-Derived Peptides and HLA Molecules Recognized by T Cells from Atopic Individuals

Mutant derivatives of the main respiratory allergen of cow are less allergenic than the intact molecule

Immunotherapy for allergies and asthma: present and future

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