FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Immunology2013; 141(1); 52-60; doi: 10.1111/imm.12166

Differential CD4+ T-cell responses of allergic and non-allergic subjects to the immunodominant epitope region of the horse major allergen Equ c 1.

Abstract: The responses of allergen-specific CD4(+) T cells of allergic and healthy individuals are still incompletely understood. Our objective was to investigate the functional and phenotypic properties of CD4(+) T cells of horse-allergic and healthy subjects specific to the immunodominant epitope region of the major horse allergen Equ c 1. Specific T-cell lines (TCLs) and clones were generated from peripheral blood mononuclear cells with Equ c 1(143-160), the peptide containing the immunodominant epitope region of Equ c 1. The frequency, proliferative response, cytokine production and HLA restriction of the cells were examined. The frequency of Equ c 1-specific CD4(+) T cells was low (approximately 1 per 10(6) CD4(+) T cells) in both allergic and non-allergic subjects. The cells of allergic subjects had a stronger proliferative capacity than those of non-allergic subjects, and they predominantly emerged from the memory T-cell pool and expressed the T helper type 2 cytokine profile, whereas the cells of non-allergic subjects emerged from the naive T-cell pool and produced low levels of interferon-γ and interleukin-10. T-cell response to Equ c 1(143-160) was restricted by several common HLA class II molecules from both DQ and DR loci. As the phenotypic and functional properties of Equ c 1-specific CD4(+) T cells differ between allergic and non-allergic subjects, allergen-specific T cells appear to be tightly implicated in the development of diseased or healthy outcome. Restriction of the specific CD4(+) T-cell response by multiple HLA alleles suggests that Equ c 1(143-160) is a promising candidate for peptide-based immunotherapy.
© 2013 John Wiley & Sons Ltd.
Get Full Text
Publication Date: 2013-09-03 PubMed ID: 23991693PubMed Central: PMC3893849DOI: 10.1111/imm.12166Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Clinical Trial
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research studied the responses of specific immune cells, known as CD4+ T cells, in people who are allergic to horses compared to those who aren’t. The study discovered that allergic individuals’ T cells reacted more strongly, suggesting a possible pathway for potential treatments for this type of allergy.

Research Objective and Methodology

  • This study aimed to closely investigate the functional and phenotypic characteristics of CD4+ T cells in individuals allergic to the major horse allergen, Equ c 1, in comparison to non-allergic individuals.
  • To achieve this, the researchers generated specific T-cell lines and clones from peripheral blood mononuclear cells with the peptide Equ c 1(143-160), which contains the allergen’s immunodominant epitope region.

Findings: Frequency, Proliferative Response, and Cytokine Production

  • The researchers observed that the frequency of Equ c 1-specific CD4+ T cells was low in both allergic and non-allergic subjects.
  • However, the cells from individuals with allergies had a stronger capacity for cell multiplication or proliferation than those from non-allergic subjects.
  • The cells from allergic subjects primarily originated from the memory T-cell pool, indicating previous exposure and immune response, and expressed a T-helper (Th2) cytokine profile. This shows a type of immune response typically associated with allergies and asthma.
  • In contrast, the cells from non-allergic subjects emerged from the naive or new T-cell pool and produced low levels of interferon-gamma and interleukin-10, which are important regulatory cytokines for immune responses.

Findings: HLA Restriction

  • The T-cell response to Equ c 1(143-160) was restricted by various common HLA (Human Leukocyte Antigen) class II molecules stemming from both DQ and DR gene loci. These HLA molecules are crucial to the immune system for distinguishing between self and non-self entities.

Implications and Conclusion

  • The study concluded that the Equ c 1-specific CD4(+) T cells from allergic and non-allergic individuals exhibited different phenotypic and functional properties which indicates that they play a significant role in the development of allergic reactions or the lack thereof.
  • The restriction of the specific T-cell response by multiple HLA alleles suggests that the peptide Equ c 1(143-160) might serve as a promising candidate for peptide-based immunotherapy, possibly suggesting a treatment pathway for this type of allergy.

Cite This Article

APA
Kailaanmäki A, Kinnunen T, Kwok WW, Rytkönen-Nissinen M, Randell J, Virtanen T. (2013). Differential CD4+ T-cell responses of allergic and non-allergic subjects to the immunodominant epitope region of the horse major allergen Equ c 1. Immunology, 141(1), 52-60. https://doi.org/10.1111/imm.12166

Publication

Immunology
ISSN: 1365-2567
NlmUniqueID: 0374672
Country: England
Language: English
Volume: 141
Issue: 1
Pages: 52-60

Researcher Affiliations

Kailaanmäki, Anssi
  • Department of Clinical Microbiology, Institute of Clinical Medicine and Biocentre Kuopio, University of Eastern Finland, Kuopio, Finland.
Kinnunen, Tuure
    Kwok, William W
      Rytkönen-Nissinen, Marja
        Randell, Jukka
          Virtanen, Tuomas

            MeSH Terms

            • Allergens / immunology
            • Animals
            • Cell Line
            • Cell Proliferation
            • Epitopes, T-Lymphocyte / immunology
            • Female
            • Glycoproteins / immunology
            • Histocompatibility Antigens Class II / immunology
            • Horses
            • Humans
            • Hypersensitivity / immunology
            • Hypersensitivity / pathology
            • Interferon-gamma / immunology
            • Interleukin-10 / immunology
            • Lipocalins
            • Male
            • Th2 Cells / immunology
            • Th2 Cells / pathology

            References

            This article includes 26 references
            1. Parviainen S, Taivainen A, Liukko A, Nieminen A, Rytkönen-Nissinen M, Kinnunen T, Virtanen T. Comparison of the allergic and nonallergic CD4+ T-cell responses to the major dog allergen Can f 1.. J Allergy Clin Immunol 2010 Aug;126(2):406-8, 408.e1-4.
              pubmed: 20624643doi: 10.1016/j.jaci.2010.06.005google scholar: lookup
            2. Kinnunen T, Nieminen A, Kwok WW, Närvänen A, Rytkönen-Nissinen M, Saarelainen S, Taivainen A, Virtanen T. Allergen-specific naïve and memory CD4+ T cells exhibit functional and phenotypic differences between individuals with or without allergy.. Eur J Immunol 2010 Sep;40(9):2460-9.
              pubmed: 20690179doi: 10.1002/eji.201040328google scholar: lookup
            3. Bateman EA, Ardern-Jones MR, Ogg GS. Persistent central memory phenotype of circulating Fel d 1 peptide/DRB1*0101 tetramer-binding CD4+ T cells.. J Allergy Clin Immunol 2006 Dec;118(6):1350-6.
              pubmed: 17137868doi: 10.1016/j.jaci.2006.07.040google scholar: lookup
            4. DeLong JH, Simpson KH, Wambre E, James EA, Robinson D, Kwok WW. Ara h 1-reactive T cells in individuals with peanut allergy.. J Allergy Clin Immunol 2011 May;127(5):1211-8.e3.
              pmc: PMC3130623pubmed: 21459424doi: 10.1016/j.jaci.2011.02.028google scholar: lookup
            5. Macaubas C, Wahlstrom J, Galvão da Silva AP, Forsthuber TG, Sønderstrup G, Kwok WW, DeKruyff RH, Umetsu DT. Allergen-specific MHC class II tetramer+ cells are detectable in allergic, but not in nonallergic, individuals.. J Immunol 2006 Apr 15;176(8):5069-77.
              pubmed: 16585604doi: 10.4049/jimmunol.176.8.5069google scholar: lookup
            6. Wambre E, DeLong JH, James EA, LaFond RE, Robinson D, Kwok WW. Differentiation stage determines pathologic and protective allergen-specific CD4+ T-cell outcomes during specific immunotherapy.. J Allergy Clin Immunol 2012 Feb;129(2):544-51, 551.e1-7.
              pmc: PMC3268867pubmed: 21975176doi: 10.1016/j.jaci.2011.08.034google scholar: lookup
            7. Kwok WW, Roti M, Delong JH, Tan V, Wambre E, James EA, Robinson D. Direct ex vivo analysis of allergen-specific CD4+ T cells.. J Allergy Clin Immunol 2010 Jun;125(6):1407-1409.e1.
              pmc: PMC3909500pubmed: 20513526doi: 10.1016/j.jaci.2010.03.037google scholar: lookup
            8. Virtanen T, Kinnunen T. Mammalian allergens.. Clin Allergy Immunol 2008;21:201-18.
              pubmed: 18828506
            9. Dandeu JP, Rabillon J, Divanovic A, Carmi-Leroy A, David B. Hydrophobic interaction chromatography for isolation and purification of Equ.cl, the horse major allergen.. J Chromatogr 1993 Nov 17;621(1):23-31.
              pubmed: 8308084doi: 10.1016/0378-4347(93)80072-cgoogle scholar: lookup
            10. Saarelainen S, Rytkönen-Nissinen M, Rouvinen J, Taivainen A, Auriola S, Kauppinen A, Kinnunen T, Virtanen T. Animal-derived lipocalin allergens exhibit immunoglobulin E cross-reactivity.. Clin Exp Allergy 2008 Feb;38(2):374-81.
              pubmed: 18070162doi: 10.1111/j.1365-2222.2007.02895.xgoogle scholar: lookup
            11. Immonen A, Kinnunen T, Sirven P, Taivainen A, Houitte D, Peräsaari J, Närvänen A, Saarelainen S, Rytkönen-Nissinen M, Maillere B, Virtanen T. The major horse allergen Equ c 1 contains one immunodominant region of T cell epitopes.. Clin Exp Allergy 2007 Jun;37(6):939-47.
              pubmed: 17517108doi: 10.1111/j.1365-2222.2007.02722.xgoogle scholar: lookup
            12. Kauppinen A, Peräsaari J, Taivainen A, Kinnunen T, Saarelainen S, Rytkönen-Nissinen M, Jeal H, Jones M, Virtanen T. Association of HLA class II alleles with sensitization to cow dander Bos d 2, an important occupational allergen.. Immunobiology 2012 Jan;217(1):8-12.
              pubmed: 21962572doi: 10.1016/j.imbio.2011.08.012google scholar: lookup
            13. Hermann R, Turpeinen H, Laine AP, Veijola R, Knip M, Simell O, Sipilä I, Akerblom HK, Ilonen J. HLA DR-DQ-encoded genetic determinants of childhood-onset type 1 diabetes in Finland: an analysis of 622 nuclear families.. Tissue Antigens 2003 Aug;62(2):162-9.
              pubmed: 12889996doi: 10.1034/j.1399-0039.2003.00071.xgoogle scholar: lookup
            14. Juntunen R, Liukko A, Taivainen A, Närvänen A, Durand G, Kauppinen A, Nieminen A, Rytkönen-Nissinen M, Saarelainen S, Maillère B, Virtanen T, Kinnunen T. Suboptimal recognition of a T cell epitope of the major dog allergen Can f 1 by human T cells.. Mol Immunol 2009 Oct;46(16):3320-7.
              pubmed: 19700193doi: 10.1016/j.molimm.2009.07.022google scholar: lookup
            15. Kinnunen T, Taivainen A, Partanen J, Immonen A, Saarelainen S, Rytkönen-Nissinen M, Rautiainen J, Virtanen T. The DR4-DQ8 haplotype and a specific T cell receptor Vbeta T cell subset are associated with absence of allergy to Can f 1.. Clin Exp Allergy 2005 Jun;35(6):797-803.
              pubmed: 15969672doi: 10.1111/j.1365-2222.2005.02247.xgoogle scholar: lookup
            16. Novak EJ, Liu AW, Nepom GT, Kwok WW. MHC class II tetramers identify peptide-specific human CD4(+) T cells proliferating in response to influenza A antigen.. J Clin Invest 1999 Dec;104(12):R63-7.
              pmc: PMC480919pubmed: 10606632doi: 10.1172/JCI8476google scholar: lookup
            17. Zeiler T, Mäntyjärvi R, Rautiainen J, Rytkönen-Nissinen M, Vilja P, Taivainen A, Kauppinen J, Virtanen T. T cell epitopes of a lipocalin allergen colocalize with the conserved regions of the molecule.. J Immunol 1999 Feb 1;162(3):1415-22.
              pubmed: 9973397
            18. Oseroff C, Sidney J, Kotturi MF, Kolla R, Alam R, Broide DH, Wasserman SI, Weiskopf D, McKinney DM, Chung JL, Petersen A, Grey H, Peters B, Sette A. Molecular determinants of T cell epitope recognition to the common Timothy grass allergen.. J Immunol 2010 Jul 15;185(2):943-55.
              pmc: PMC3310373pubmed: 20554959doi: 10.4049/jimmunol.1000405google scholar: lookup
            19. Van Overtvelt L, Wambre E, Maillère B, von Hofe E, Louise A, Balazuc AM, Bohle B, Ebo D, Leboulaire C, Garcia G, Moingeon P. Assessment of Bet v 1-specific CD4+ T cell responses in allergic and nonallergic individuals using MHC class II peptide tetramers.. J Immunol 2008 Apr 1;180(7):4514-22.
              pubmed: 18354173doi: 10.4049/jimmunol.180.7.4514google scholar: lookup
            20. Wambre E, James EA, Kwok WW. Characterization of CD4+ T cell subsets in allergy.. Curr Opin Immunol 2012 Dec;24(6):700-6.
              pmc: PMC3729480pubmed: 22889592doi: 10.1016/j.coi.2012.07.009google scholar: lookup
            21. Pala P, Message SD, Johnston SL, Openshaw PJ. Increased aeroallergen-specific interleukin-4-producing T cells in asthmatic adults.. Clin Exp Allergy 2002 Dec;32(12):1739-44.
              pubmed: 12653165doi: 10.1046/j.1365-2222.2002.01548.xgoogle scholar: lookup
            22. Ling EM, Smith T, Nguyen XD, Pridgeon C, Dallman M, Arbery J, Carr VA, Robinson DS. Relation of CD4+CD25+ regulatory T-cell suppression of allergen-driven T-cell activation to atopic status and expression of allergic disease.. Lancet 2004 Feb 21;363(9409):608-15.
              pubmed: 14987885doi: 10.1016/S0140-6736(04)15592-Xgoogle scholar: lookup
            23. Skrindo I, Farkas L, Kvale EO, Johansen FE, Jahnsen FL. Depletion of CD4+CD25+CD127lo regulatory T cells does not increase allergen-driven T cell activation.. Clin Exp Allergy 2008 Nov;38(11):1752-9.
              pubmed: 18681851doi: 10.1111/j.1365-2222.2008.03081.xgoogle scholar: lookup
            24. Walker SM, Durham SR, Till SJ, Roberts G, Corrigan CJ, Leech SC, Krishna MT, Rajakulasingham RK, Williams A, Chantrell J, Dixon L, Frew AJ, Nasser SM. Immunotherapy for allergic rhinitis.. Clin Exp Allergy 2011 Sep;41(9):1177-200.
              pubmed: 21848757doi: 10.1111/j.1365-2222.2011.03794.xgoogle scholar: lookup
            25. Klitz W, Maiers M, Spellman S, Baxter-Lowe LA, Schmeckpeper B, Williams TM, Fernandez-Viña M. New HLA haplotype frequency reference standards: high-resolution and large sample typing of HLA DR-DQ haplotypes in a sample of European Americans.. Tissue Antigens 2003 Oct;62(4):296-307.
              pubmed: 12974796doi: 10.1034/j.1399-0039.2003.00103.xgoogle scholar: lookup
            26. Jahn-Schmid B, Wopfner N, Hubinger G, Asero R, Ebner C, Ferreira F, Bohle B. The T-cell response to Amb a 1 is characterized by 3 dominant epitopes and multiple MHC restriction elements.. J Allergy Clin Immunol 2010 Nov;126(5):1068-71, 1071.e1-2.
              pubmed: 20638115doi: 10.1016/j.jaci.2010.05.038google scholar: lookup

            Citations

            This article has been cited 3 times.
            1. Grifoni A, da Silva Antunes R, Westernberg L, Pham J, Birrueta G, Peters B, Sette A, Schulten V. Characterization and epitope identification of the T cell response in non-allergic individuals exposed to mouse allergen. World Allergy Organ J 2019;12(4):100026.
              doi: 10.1016/j.waojou.2019.100026pubmed: 31044023google scholar: lookup
            2. Virtanen T. Reply to the letter to the editor concerning the review Immunotherapy for pet allergies. Hum Vaccin Immunother 2018 Jun 3;14(6):1442-1443.
              doi: 10.1080/21645515.2018.1449554pubmed: 29533130google scholar: lookup
            3. Hentges F, Léonard C, Arumugam K, Hilger C. Immune responses to inhalant Mammalian allergens. Front Immunol 2014;5:234.
              doi: 10.3389/fimmu.2014.00234pubmed: 24904583google scholar: lookup
            Subscribe to our newsletter
            Join 99,780 horse owners like you who receive our email updates on horse health and nutrition.