Equipe Immunochimie de la réponse immunitaire cellulaire
CEA Saclay/Bât 152
Tél : 01 69 08 94 47
bernard.maillere@cea.fr
Notre équipe travaille sur la caractérisation de la réponse immunitaire cellulaire et l’identification des séquences immunogéniques des protéines (ou épitopes T).
Moyens humains
Bernard MAILLERE, Chercheur
Florence CASTELLI, Chercheuse
Stéphanie DELLUC, Chercheuse
Aurélie SCHNEIDER, Ingénieure
Emmanuel FAVRY, Technicien supérieur
Carolyne GRYGAR, Technicienne CDD
Nicolas COUTURIER, Chercheur Postdoctotal
Claire CHEVALEYRE, Doctorante
Thèmes de recherche
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Modèle de fixation d’un peptide épitope T CD4+ sur la molécule HLA-DR1
Les épitopes T CD4+ sont des peptides de 13 à 25 acides amines qui sont reconnus par les lymphocytes T CD4+. Ils résultent de la dégradation des antigènes qui se produit dans les cellules présentatrices et sont présentés aux cellules T par les molécules HLA II. Les épitopes T CD4+ se fixent aux molécules HLA II par les résidus d’ancrage qui sont accommodés par les cinq poches de spécificité des molécules HLA II localisées en P1, P4, P6 P7 et P9 |
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© CEA/B. Maillère |
Les épitopes T sont les peptides que reconnaissent les lymphocytes T. Les lymphocytes T CD8+ ont une activité cytotoxique et reconnaissent les antigènes sous la forme de peptides que leur présentent les molécules HLA de classe I. Les lymphocytes T CD4+ interviennent sur la régulation, positive ou négative de la réponse immunitaire et reconnaissent les antigènes sous la forme de peptides que leur présentent les molécules HLA de classe II.
En raison du rôle majeur des lymphocytes T dans l’immunité, les épitopes T constituent d’intéressantes molécules pour le diagnostic cellulaire et la vaccination. Toutefois, compte tenu du polymorphisme des molécules HLA, les épitopes T varient d'un individu à un autre ce qui limite leur utilisation clinique. Leur identification nécessite des outils appropriés qui tiennent compte du polymorphisme des molécules HLA.
Mots-clés
HLA II, peptides, vaccin, allergène, virus, tumeur, test de liaison
Publications
Ascough S, Ingram RJ, Metan G, Maillère B, Doganay M, Ozkul Y, Kim LU, Ballie L, Moore S, Huwar TB, Sriskandan S, Altmann DM. (2012). Comment on "Frequency of epitope-specific naive CD4+ T cells correlates with immunodominance in the human memory repertoire. J Immunol. 188, 5205-5206.
Godet Y, Fabre E, Dosset M, Lamuraglia M, Levionnois E, Ravel P, Benhamouda N, Cazes A, Le Pimpec-Barthes F, Gaugler B, Langlade-Demoyen P, Pivot X, Saas P, Maillère B, Tartour E, Borg C, Adotévi O. (2012). Analysis of spontaneous tumor-specific CD4 T-cell immunity in lung cancer using promiscuous HLA-DR telomerase-derived epitopes: potential synergistic effect with chemotherapy response. Clin Cancer Res. 18, 2943-2953.
Knapp B, Fischer G, Van Hemelen D, Fae I, Maillère B, Ebner C, Schreiner W, Bohle B, Jahn-Schmid B. (2012). Association of HLA-DR1 with the allergic response to the major mugwort pollen allergen: molecular background. BMC Immunol. doi: 10.1186/1471-2172-13-43.
Maillère B, Delluc S, Ravot G. (2012). The prediction of immunogenicity of therapeutic proteins. Med Sci (Paris). 28, 82-88.
Ru Z T, Xiao W J, Pajot A, Kou Z H, Sun S H, Maillère B, Zhao G Y, Ojcius D M, Lone Y C, Zhou Y S. (2012). Development of a Humanized HLA-A2.1/DP4 Transgenic Mouse Model and the Use of This Model to Map HLA-DP4-Restricted Epitopes of HBV Envelope Protein. PLoS ONE. 7, e32247.
Zuidmeer-Jongejan L, Fernandez-Rivas M, Poulsen LK, Neubauer A, Asturias J, Blom L, Boye J, Bindslev-Jensen C, Clausen M, Ferrara R, Garosi P, Huber H, Jensen BM, Koppelman S, Kowalski ML, Lewandowska-Polak A, Linhart B, Maillère B, Mari A, Martinez A, Mills CE, Nicoletti C, Opstelten DJ, Papadopoulos NG, Portoles A, Rigby N, Scala E, Schnoor HJ, Sigursdottir S, Stavroulakis G, Stolz F, Swoboda I, Valenta R, van den Hout R, Versteeg SA, Witten M, van Ree R. (2012). FAST: towards safe and effective subcutaneous immunotherapy of persistent life-threatening food allergies. Clin Transl Allergy. 2, 5.
Bernardeau K, Kerzhero J, Fortun A, Moreau-Aubry A, Favry E, Echasserieau K, Tartour E, Maillère B, Lang F. (2011). A simple competitive assay to determine peptide affinity for HLA class II molecules: A useful tool for epitope prediction. J Immunol Methods. 371, 97-105.
Chu K K, Tippayawat P, Walker N J, Harding S V, Atkins H S, Maillère B, Bancroft G J, Lertmemongkolchai G, Altmann D M. (2011). CD4+ T-cell immunity to the Burkholderia pseudomallei ABC transporter LolC in melioidosis. Eur J Immunol. 41, 107-115.
Delluc S, Ravot G, Maillère B. (2011). Quantitative analysis of the CD4 T-cell repertoire specific to therapeutic antibodies in healthy donors. FASEB J. 25, 2040-2048.
Kudela P, Sun Z, Fourcade J, Janjic B, Kirkwood J M, Maillère B, Zarour H M. (2011). Epitope hierarchy of spontaneous CD4+ T cell responses to LAGE-1. J Immunol. 186, 312-322.
Tartour E, Pere H, Maillère B, Terme M, Merillon N, Taieb J, Sandoval F, Quintin-Colonna F, Lacerda K, Karadimou A, Badoual C, Tedgui A, Fridman W H, Oudard S. (2011). Angiogenesis and immunity: a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy. Cancer Metastasis Rev. 30, 83-95.
Wambre E, Bonvalet M, Bodo V B, Maillère B, Leclert G, Moussu H, Von Hofe E, Louise A, Balazuc A M, Ebo D, Hoarau C, Garcia G, Van Overtvelt L, Moingeon P. (2011). Distinct characteristics of seasonal (Bet v 1) vs. perennial (Der p 1/Der p 2) allergen-specific CD4(+) T cell responses. Clin Exp Allergy. 41, 192-203.
Worm M, Lee H H, Kleine-Tebbe J, Hafner R P, Laidler P, Healey D, Buhot C, Verhoef A, Maillère B, Kay A B, Larche M. (2011). Development and preliminary clinical evaluation of a peptide immunotherapy vaccine for cat allergy. J Allergy Clin Immunol. 127, 89-97, 97 e1-14.
Bourgault Villada I, Moyal Barracco M, Berville S, Bafounta ML, Longvert C, Prémel V, Villefroy P, Jullian E, Clerici T, Paniel B, Maillère B, Choppin J, Guillet JG. (2010). Human papillomavirus 16-specific T cell responses in classic HPV-related vulvar intra-epithelial neoplasia. Determination of strongly immunogenic regions from E6 and E7 proteins. Clin. Exp. Immunol. 159, 45-56.
Chabre H, Gouyon B, Huet A, Boran-Bodo V, Nony E, Hrabina M, Fenaille F, Lautrette A, Bonvalet M, Maillère B, Bordas-Le Floch V, Van Overtvelt L, Jain K, Ezan E, Batard T, Moingeon P. (2010). Molecular variability of group 1 and 5 grass pollen allergens between Pooldeae species: implications for immunotherapy. Clin. Exp. Allergy. 40, 505-519.
Delluc S, Ravot G, Maillère B. (2010). Quantification of the pre-existing CD4 T cell repertoire specific for human erythropoietin reveals its immunogenicity potential. Blood. 116, 4542-4545.
Ingram R J, Chu K K, Metan G, Maillère B, Doganay M, Ozkul Y, Dyson H, Williamson E D, Baillie L, Kim L U, Ascough S, Sriskandan S, Altmann D M. (2010). An Epitope of Bacillus anthracis Protective Antigen That Is Cryptic in Rabbits May Be Immunodominant in Humans. Infect Immun. 78, 2353-2353.
Ingram R J, Metan G, Maillère B, Doganay M, Ozkul Y, Kim L U, Baillie L, Dyson H, Williamson E D, Chu K K, Ascough S, Moore S, Huwar T B, Robinson J H, Sriskandan S, Altmann D M. (2010). Natural Exposure to Cutaneous Anthrax Gives Long-Lasting T Cell Immunity Encompassing Infection-Specific Epitopes. J Immunol. 184, 3814-3821.
Kerzerho J, Adotevi O, Castelli F, Dosset M, Bernardeau K, Szely N, Lang F, Tartour E, and Maillère B. (2010). The Angiogenic Growth Factor and Biomarker Midkine Is a Tumor-Shared Antigen, The Journal of Immunology. 185, 418-423.
Musson JA, Ingram R, Durand G, Ascough S, Waters EL, Hartley MG, Robson T, Maillère B, Williamson ED, Sriskandan S, Altmann D, Robinson JH. (2010). Repertoire of HLA-DR1-restricted CD4 T-cell responses to capsular Caf1 antigen of Yersinia pestis in human leukocyte antigen transgenic mice. Infect Immun. 78, 4356-62.
Villada I B, Barracco M M, Berville S, Bafounta M L, Longvert C, Premel V, Villefroy P, Jullian E, Clerici T, Paniel B, Maillère B, Choppin J, Guillet J G. (2010). Human papillomavirus 16-specific T cell responses in classic HPV-related vulvar intra-epithelial neoplasia. Determination of strongly immunogenic regions from E6 and E7 proteins. Clin Exp Immunol. 159, 45-56.
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. (2009). Suboptimal recognitin of a T cell epitope of the major dog allergen Can f1 by human T cells. Mol. Immunol. 46, 3320-3327.
Knapp B, Omasits U, Bohle B, Maillère B, Ebner C, Schreiner W, Jahn-Schmid B. (2009). 3-Layer-based analysis of peptide-MHC interaction: In silico prediction, peptide binding affinity and T cell activation in a relevant allergen-specific model. Mol Immunol. 46, 1839-44.
Sirven P, Castelli FA, Probst A, Szely N, Maillère B. (2009). In vitro human CD4+ T cell response to the vaccinia protective antigens B5R and A33R. Mol Immunol. 6, 1481-7.
Castelli FA, Houitte D, Munier G, Szely N, Lecoq A, Briand JP, Muller S, Maillère B. (2008). Immunoprevalence of the CD4(+) T-cell response to HIV Tat and Vpr proteins is provided by clustered and disperse epitopes, respectively. Eur J Immunol. 38, 2821-31.
Chentoufi AA, Binder NR, Berka N, Durand G, Nguyen A, Bettahi I, Maillère B, Benmohamed L. (2008). Asymptomatic Human CD4+ Cytotoxic T-Cell Epitopes Identified from Herpes Simplex Virus Glycoprotein B. J Virol. 82, 11792-802.
Jahn-Schmid B, Sirven P, Leb V, Pickl WF, Fischer GF, Gadermaier G, Egger M, Ebner C, Ferreira F, Maillère B, Bohle B. (2008). Characterization of HLA class II/peptide-TCR interactions of the immunodominant T cell epitope in Art v 1, the major mugwort pollen allergen. J Immunol. 181, 3636-42.
Oseroff C, Peters B, Pasquetto V, Moutaftsi M, Sidney J, Panchanathan V, Tscharke DC, Maillère B, Grey H, Sette A. (2008). Dissociation between Epitope Hierarchy and Immunoprevalence in CD8 Responses to Vaccinia Virus Western Reserve. J Immunol. 180, 7193-202.
Prost S, Le Dantec M, Augé S, Le Grand R, Derdouch S, Auregan G, Déglon N, Relouzat F, Aubertin AM, Maillère B, Dusanter-Fourt I, Kirszenbaum M. (2008). Nef and PPAR-gamma interact to suppress Stat5 expression in CD34+ progenitors from infected macaques. Med Sci (Paris). 24, 551-554.
Prost S, Le Dantec M, Augé S, Le Grand R, Derdouch S, Auregan G, Déglon N, Relouzat F, Aubertin AM, Maillère B, Dusanter-Fourt I, Kirszenbaum M. (2008). Human and simian immunodeficiency viruses deregulate early hematopoiesis through a Nef/PPARgamma/STAT5 signaling pathway in macaques. J Clin Invest. 118, 1765-1775.
Saarelainen SA, Kinnunen TT, Buhot C, Närvänen AT, Kauppinen AK, Rytkönen-Nissinen MA, Maillère B, Virtanen TI. (2008). Immunotherapeutic potential of the immunodominant T-cell epitope of lipocalin allergen Bos d 2 and its analogues. Immunology. 123, 358-66.
Van Overtvelt L, Wambre E, Maillère B, von Hofe E, Louise A, Balazuc AM, Bohle B, Ebo D, Leboulaire C, Garcia G, Moingeon P. (2008). Assessment of Bet v 1-Specific CD4+ T Cell Responses in Allergic and Nonallergic Individuals Using MHC Class II Peptide Tetramers. J Immunol. 180, 4514-22.
Wambre E, Van Overtvelt L, Maillère B, Humphreys R, von Hofe E, Ferhat L, Ebo D, Moingeon P. (2008). Single Cell Assessment of Allergen-Specific T Cell Responses with MHC Class II Peptide Tetramers: Methodological Aspects. Int Arch Allergy Immunol. 146, 99-112.
Wang XF, Kerzerho J, Adotevi O, Nuyttens H, Badoual C, Munier G, Oudard S, Tu S, Tartour E, Maillère B. (2008). Comprehensive Analysis of HLA-DR- and HLA-DP4-Restricted CD4+ T Cell Response Specific for the Tumor-Shared Antigen Survivin in Healthy Donors and Cancer Patients. J Immunol. 181, 431-9.
Zhang X, Castelli FA, Zhu X, Wu M, Maillère B, Benmohamed L. (2008). Gender-Dependent Human Leukocyte Antigen (HLA)-DR-Restricted Epitopes Identified from the Herpes Simplex Virus Type 1 Glycoprotein D. Clin Vaccine Immunol. 5, 1436-49.
Castelli FA, Leleu M, Pouvelle-Moratille S, Farci S, Zarour HM, Andrieu M, Auriault C, Menez A, Georges B, Maillere B. (2007).Differential capacity of T cell priming in naive donors of promiscuous CD4(+) T cell epitopes of HCV NS3 and Core proteins. Eur J Immunol. 37,1513-23.
Depil S, Morales O, Castelli FA, Delhem N, Francois V, Georges B, Dufosse F, Morschhauser F, Hammer J, Maillère B, Auriault C, Pancre V. (2007).Determination of a HLA II promiscuous peptide cocktail as potential vaccine against EBV latency II malignancies. J Immunother. 30, 215-226.
Gahery H, Figueiredo S, Texier C, Pouvelle-Moratille S, Ourth L, Igea C, Surenaud M, Guillet JG, Maillère B. (2007). HLA-DR-Restricted Peptides Identified in The Nef Protein Can Induce HIV Type 1-Specific IL-2/IFN-gamma-Secreting CD4(+) And CD4(+) /CD8(+) T Cells in Humans after Lipopeptide Vaccination. AIDS Res Hum Retroviruses. 23, 427-437.
Hanvesakul R, Maillère B, Briggs D, Baker R, Larche M, Ball S. (2007). Indirect Recognition of T-Cell Epitopes Derived from the alpha3 and Transmembrane Domain of HLA-A2. Am J Transplant. 7, 1148-57.
Immonen A, Kinnunen T, Sirven P, Taivainen A, Houitte D, Perasaari J, Narvanen A, Saarelainen S, Rytkonen-Nissinen M, Maillere B, Virtanen T. (2007)The major horse allergen Equ c 1 contains one immunodominant region of T cell epitopes. Clin Exp Allergy. 37, 939-47.
Kudela P, Janjic B, Fourcade J, Castelli F, Andrade P, Kirkwood JM, El-Hefnawy T, Amicosante M, Maillère B, Zarour HM. (2007).Cross-Reactive CD4+ T Cells against One Immunodominant Tumor-Derived Epitope in Melanoma Patients. J Immunol. 179, 7932-40.
Malmassari SL, Deng Q, Fontaine H, Houitte D, Rimlinger F, Thiers V, Maillère B, Pol S, Michel ML. (2007). Impact of hepatitis B virus basic core promoter mutations on T cell response to an immunodominant HBx-derived epitope. Hepatology. 45, 1199-1209.
Saarelainen SA, Kinnunen TT, Buhot C, Närvänen AT, Kauppinen AK, Rytkönen-Nissinen MA, Maillère B, Virtanen TI. (2007).Immunotherapeutic potential of the immunodominant T-cell epitope of lipocalin allergen Bos d 2 and its analogues. Immunology. 123, 358-66.
Wang XF, Cohen WM, Castelli FA, Almunia C, Lethe B, Pouvelle-Moratille S, Munier G, Charron D, Ménez A, Zarour HM, Van Der Bruggen P, Busson M, Maillère B. (2007).Selective identification of HLA-DP4 binding T cell epitopes encoded by the MAGE-A gene family. Cancer Immunol Immunother. 56, 807-818.
Busson M, Castelli FA, Wang XF, Cohen WM, Charron D, Ménez A, Maillère B. (2006). Prediction of CD4+ T cell epitopes restricted to HLA-DP4 molecules. J Immunol Methods. 317, 144-151.
Cohen WM, Pouvelle-Moratille S, Wang XF, Farci S, Munier G, Charron D, Ménez A, Busson M, Maillère B. (2006). Scanning the HIV genome for CD4+ T cell epitopes restricted to HLA-DP4, the most prevalent HLA class II molecule. J Immunol. 176, 5401-5408.
Depil S, Angyalosi G, Moralès O, Delacre M, Delhem N, François V, Georges B, Hammer J, Maillère B, Auriault C, Pancré V. (2006). Peptide-binding assays and HLA II transgenic Aß° mice are consistent and complementary tools for identifying HLA II-restricted peptides Vaccine. 24, 2225-2229.
Janjic B, Andrade P, Wang XF, Fourcade J, Almunia C, Kudela P, Brufsky A, Jacobs S, Friedland D, Stoller R, Gillet D, Herberman RB, Kirkwood JM, Maillère B,Zarour HM. (2006). Spontaneous CD4+ T cell responses against TRAG-3 in patients with melanoma and breast cancers. J Immunol. 177, 2717-2727.
Mouquet H, Farci S, Joly P, Maillère B, Leblond J, Drouot L, Leprince J, Tonon MC, Loiseau P, Charron D, Tron F, Gilbert D. (2006). A truncated alternative spliced isoform of human desmoglein 1 contains a specific T cell epitope binding to the pemphigus foliaceus-associated HLA class II DRbeta1*0102 molecule. J Immunol. 177, 6517-6526.
Tarzi M, Klunker S, Texier C, Verhoef A, Stapel SO, Akdis CA, Maillère B, Kay AB, Larche M. (2006). Induction of interleukin-10 and suppressor of cytokine signalling-3 gene expression following peptide immunotherapy. Clin Exp Allergy. 36, 465-474.
Wang XF, Cohen WM, Castelli FA, Almunia C, Lethe B, Pouvelle-Moratille S, Munier G, Charron D, Ménez A, Zarour HM, Van Der Bruggen P, Busson M, Maillère B. (2006). Selective identification of HLA-DP4 binding T cell epitopes encoded by the MAGE-A gene family. Cancer Immunol Immunother. 56, 807-818.
Babon A, Almunia C, Boccaccio C, Beaumelle B, Gelb MH, Ménez A, Maillère B, Abastado JP, Salcedo M, Gillet D. (2005). Cross-presentation of a CMV pp65 epitope by human dendritic cells using bee venom PLA2 as a membrane-binding vector FEBS Lett. 579, 1658-1664.
Mandic M, Castelli F, Janjic B, Almunia C, Andrade P, Gillet D, Brusic V, Kirkwood JM, Maillère B, Zarour HM. (2005). One NY-ESO-1-derived epitope that promiscuously binds to multiple HLA-DR and HLA-DP4 molecules and stimulates autologous CD4+ T cells from patients with NY-ESO-1-expressing melanoma. J Immunol. 174, 1751-1759.
Bourgault Villada I, Moyal Barracco M, Ziol M, Chaboissier A, Barget N, Berville S, Paniel B, Jullian E, Clerici T, Maillère B, Guillet JG. (2004). Spontaneous regression of grade 3 vulvar intraepithelial neoplasia associated with human papillomavirus-16-specific CD4(+) and CD8(+) T-cell responses. Cancer Res. 64, 8761-8766.
Buhot C, Chenal A, Sanson A, Pouvelle-Moratille S, Gelb MH, Ménez A, Gillet D, Maillère B. (2004). Alteration of the tertiary structure of the major bee venom allergen Api m 1 by multiple mutations is concomitant with low IgE reactivity. Protein Sci.13, 2970-2978.
Lemaitre F, Viguier M, Cho MS, Fourneau JM, Maillère B, Kourilsky P, Van Endert PM, Ferradini L. (2004). Detection of low-frequency human antigen-specific CD4(+) T cells using MHC class II multimer bead sorting and immunoscope analysis. Eur J Immunol.34, 2941-2949.
Maillère B.(2004). Le renouveau des peptides en vaccinologie Biofutur. 245, 47-49. Fournel S, Neichel S, Dali H, Farci S, Maillère B, Briand JP, Muller S. (2003). CD4+ T cells from (New Zealand Black x New Zealand White)F1 lupus mice and normal mice immunized against apoptotic nucleosomes recognize similar Th cell epitopes in the C terminus of histone H3. J Immunol. 171, 636-644.
Jacquemin M, Vantomme V, Buhot C, Lavend'homme R, Burny W, Demotte N, Chaux P, Peerlinck K, Vermylen J, Maillère B, van der Bruggen P, Saint-Remy JM. (2003). CD4+ T-cell clones specific for wild-type factor VIII: a molecular mechanism responsible for a higher incidence of inhibitor formation in mild/moderate hemophilia A. Blood. 101, 1351-1358.
Kinnunen T, Buhot C, Narvanen A, Rytkonen-Nissinen M, Saarelainen S, Pouvelle-Moratille S, Rautiainen J, Taivainen A, Maillère B, Mantyjarvi R, Virtanen T. (2003). The immunodominant epitope of lipocalin allergen Bos d 2 is suboptimal for human T cells. Eur J Immunol. 33, 1717-1726.
Maillère B, Buhot C, Texier C, Pouvelle-Moratille S, Ménez A, Gillet D.(2003). Modified peptides and recombinant proteins derived from the major bee venom allergen PLA2. Rev Fr Allergol Immunol Clin. 43, 53-55.
Mandic M, Almunia C, Vicel S, Gillet D, Janjic B, Coval K, Maillère B, Kirkwood JM, Zarour HM. (2003). The alternative open reading frame of LAGE-1 gives rise to multiple promiscuous HLA-DR-restricted epitopes recognized by T-helper 1-type tumor-reactive CD4+ T cells. Cancer Res. 63, 6506-6515.
Zhang Y, Chaux P, Stroobant V, Eggermont AM, Corthals J, Maillère B, Thielemans K, Marchand M, Boon T, Van Der Bruggen P. (2003). A MAGE-3 peptide presented by HLA-DR1 to CD4+ T cells that were isolated from a melanoma patient vaccinated with a MAGE-3 protein. J Immunol. 171, 219-225.