{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T12:43:26Z","timestamp":1789389806452,"version":"build-2803163510"},"reference-count":57,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2014,6,1]],"date-time":"2014-06-01T00:00:00Z","timestamp":1401580800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2014,6,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>We show that Leishmania donovani\u2013infected macrophages (M\u03a6s) are capable of stimulating MHC class II (MHC-II)\u2013restricted T cells at 6 h of infection. At 48 h, infected M\u03a6s (I-M\u03a6s) failed to stimulate MHC-II\u2013restricted T cells but not MHC class I\u2013restricted ones, in contrast to normal M\u03a6s. Such I-M\u03a6s could stimulate T cells at a higher Ag concentration, indicating that general Ag processing and trafficking of peptide\u2013MHC-II complexes are not defective. Analysis of the kinetic parameters, like \u201ckon\u201d and \u201ckoff,\u201d showed that peptide\u2013MHC-II complex formation is compromised in I-M\u03a6s compared with normal M\u03a6s. This indicates interference in loading of the cognate peptide to MHC-II, which may be due to the presence of a noncognate molecule. This notion received support from the finding that exposure of I-M\u03a6s to low pH or treatment with 2-(1-adamantyl)-ethanol, a molecule that favors peptide exchange, led to T cell activation. When treated with 2-(1-adamantyl)-ethanol, splenocytes from 8 wk\u2013infected BALB\/c mice showed significantly higher antileishmanial T cell expansion in vitro compared with untreated controls. Hence, it is tempting to speculate that high, but not low, concentrations of cognate peptide may favor peptide exchange in I-M\u03a6s, leading to expansion of the antileishmanial T cell repertoire. The results suggest that a high Ag dose may overcome compromised T cell responses in visceral leishmaniasis, and this has an important implication in therapeutic vaccine design.<\/jats:p>","DOI":"10.4049\/jimmunol.1302970","type":"journal-article","created":{"date-parts":[[2014,5,22]],"date-time":"2014-05-22T03:34:44Z","timestamp":1400729684000},"page":"5873-5880","source":"Crossref","is-referenced-by-count":17,"title":["Class II MHC\/Peptide Interaction in <i>Leishmania donovani<\/i> Infection: Implications in Vaccine Design"],"prefix":"10.1093","volume":"192","author":[{"given":"Koushik","family":"Roy","sequence":"first","affiliation":[{"name":"Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology , Kolkata 700032,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kshudiram","family":"Naskar","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology , Kolkata 700032,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moumita","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology , Kolkata 700032,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syamal","family":"Roy","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunology Division, CSIR-Indian Institute of Chemical Biology , Kolkata 700032,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2014,6,15]]},"reference":[{"key":"2025032404355616600_r1","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1002\/eji.1830220813","article-title":"Immunobiological studies on experimental visceral leishmaniasis. II. Adherent cell-mediated down-regulation of delayed-type hypersensitivity response and up-regulation of B cell activation","volume":"22","author":"Basak","year":"1992","journal-title":"Eur. J. Immunol."},{"key":"2025032404355616600_r2","doi-asserted-by":"crossref","first-page":"e1514","DOI":"10.1371\/journal.pntd.0001514","article-title":"Molecular mechanisms of drug resistance in natural Leishmania populations vary with genetic background","volume":"6","author":"Decuypere","year":"2012","journal-title":"PLoS Negl. Trop. Dis."},{"key":"2025032404355616600_r3","doi-asserted-by":"crossref","first-page":"135","DOI":"10.4103\/0974-777X.62876","article-title":"Immunological perspectives of leishmaniasis","volume":"2","author":"Nyl\u00e9n","year":"2010","journal-title":"J. Glob. Infect. Dis."},{"key":"2025032404355616600_r4","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1111\/j.0105-2896.2004.00188.x","article-title":"The immunopathology of experimental visceral leishmaniasis","volume":"201","author":"Kaye","year":"2004","journal-title":"Immunol. Rev."},{"key":"2025032404355616600_r5","doi-asserted-by":"crossref","first-page":"e1001154","DOI":"10.1371\/journal.ppat.1001154","article-title":"Direct visualization of peptide\/MHC complexes at the surface and in the intracellular compartments of cells infected in vivo by Leishmania major","volume":"6","author":"Muraille","year":"2010","journal-title":"PLoS Pathog."},{"key":"2025032404355616600_r6","doi-asserted-by":"crossref","first-page":"3992","DOI":"10.4049\/jimmunol.168.8.3992","article-title":"CD8+ T cells are required for primary immunity in C57BL\/6 mice following low-dose, intradermal challenge with Leishmania major","volume":"168","author":"Belkaid","year":"2002","journal-title":"J. Immunol."},{"key":"2025032404355616600_r7","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1084\/jem.20040172","article-title":"Low dose Leishmania major promotes a transient T helper cell type 2 response that is down-regulated by interferon gamma-producing CD8+ T cells","volume":"199","author":"Uzonna","year":"2004","journal-title":"J. Exp. Med."},{"key":"2025032404355616600_r8","doi-asserted-by":"crossref","first-page":"4916","DOI":"10.4049\/jimmunol.174.8.4916","article-title":"Prevention of relapse after chemotherapy in a chronic intracellular infection: mechanisms in experimental visceral leishmaniasis","volume":"174","author":"Murray","year":"2005","journal-title":"J. Immunol."},{"key":"2025032404355616600_r9","doi-asserted-by":"crossref","first-page":"2530","DOI":"10.4049\/jimmunol.1200994","article-title":"CD4+ T cell-dependent IFN-\u03b3 production by CD8+ effector T cells in Mycobacterium tuberculosis infection","volume":"189","author":"Bold","year":"2012","journal-title":"J. Immunol."},{"key":"2025032404355616600_r10","doi-asserted-by":"crossref","first-page":"e1874","DOI":"10.1371\/journal.pntd.0001874","article-title":"Cytokine responses to novel antigens in an Indian population living in an area endemic for visceral leishmaniasis","volume":"6","author":"Singh","year":"2012","journal-title":"PLoS. Negl. Trop. Dis."},{"key":"2025032404355616600_r11","doi-asserted-by":"crossref","first-page":"1066","DOI":"10.1002\/eji.200838773","article-title":"IL-10 interferes directly with TCR-induced IFN-gamma but not IL-17 production in memory T cells","volume":"39","author":"Naundorf","year":"2009","journal-title":"Eur. J. Immunol."},{"key":"2025032404355616600_r12","doi-asserted-by":"crossref","first-page":"8676","DOI":"10.1073\/pnas.89.18.8676","article-title":"Interleukin 10 inhibits macrophage microbicidal activity by blocking the endogenous production of tumor necrosis factor alpha required as a costimulatory factor for interferon gamma-induced activation","volume":"89","author":"Oswald","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404355616600_r13","doi-asserted-by":"crossref","first-page":"1630","DOI":"10.1126\/science.277.5332.1630","article-title":"STATs and gene regulation","volume":"277","author":"Darnell","year":"1997","journal-title":"Science"},{"key":"2025032404355616600_r14","doi-asserted-by":"crossref","first-page":"e1002229","DOI":"10.1371\/journal.ppat.1002229","article-title":"Restoration of IFN\u03b3R subunit assembly, IFN\u03b3 signaling and parasite clearance in Leishmania donovani infected macrophages: role of membrane cholesterol","volume":"7","author":"Sen","year":"2011","journal-title":"PLoS Pathog."},{"key":"2025032404355616600_r15","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S0035-9203(96)90537-4","article-title":"Blood, bone marrow and splenic lymphocyte subset profiles in Indian visceral leishmaniasis","volume":"90","author":"Rohtagi","year":"1996","journal-title":"Trans. R. Soc. Trop. Med. Hyg."},{"key":"2025032404355616600_r16","doi-asserted-by":"crossref","first-page":"e1000805","DOI":"10.1371\/journal.ppat.1000805","article-title":"Dynamic imaging of experimental Leishmania donovani-induced hepatic granulomas detects Kupffer cell-restricted antigen presentation to antigen-specific CD8 T cells","volume":"6","author":"Beattie","year":"2010","journal-title":"PLoS Pathog."},{"key":"2025032404355616600_r17","doi-asserted-by":"crossref","first-page":"3968","DOI":"10.1128\/IAI.66.8.3968-3970.1998","article-title":"Effective and long-lasting immunity against the parasite Leishmania major in CD8-deficient mice","volume":"66","author":"Huber","year":"1998","journal-title":"Infect. Immun."},{"key":"2025032404355616600_r18","doi-asserted-by":"crossref","first-page":"1448","DOI":"10.1126\/science.8367726","article-title":"Helper T cells without CD4: control of leishmaniasis in CD4-deficient mice","volume":"261","author":"Locksley","year":"1993","journal-title":"Science"},{"key":"2025032404355616600_r19","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.4049\/jimmunol.1103554","article-title":"MHC class Ib-restricted CD8 T cells differ in dependence on CD4 T cell help and CD28 costimulation over the course of mouse polyomavirus infection","volume":"188","author":"Hofstetter","year":"2012","journal-title":"J. Immunol."},{"key":"2025032404355616600_r20","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/nature01441","article-title":"CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes","volume":"421","author":"Janssen","year":"2003","journal-title":"Nature"},{"key":"2025032404355616600_r21","doi-asserted-by":"crossref","first-page":"2834","DOI":"10.4049\/jimmunol.172.5.2834","article-title":"CD4 T cell-dependent CD8 T cell maturation","volume":"172","author":"Khanolkar","year":"2004","journal-title":"J. Immunol."},{"key":"2025032404355616600_r22","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1086\/382032","article-title":"In vitro human memory CD8 T cell expansion in response to cytomegalovirus requires CD4+ T cell help","volume":"189","author":"Salkowitz","year":"2004","journal-title":"J. Infect. Dis."},{"key":"2025032404355616600_r23","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1093\/intimm\/dxl025","article-title":"CD4+ T cell-independent maintenance and expansion of memory CD8+ T cells derived from in vitro dendritic cell activation","volume":"18","author":"Shi","year":"2006","journal-title":"Int. Immunol."},{"key":"2025032404355616600_r24","doi-asserted-by":"crossref","first-page":"2050","DOI":"10.4049\/jimmunol.151.4.2050","article-title":"Antigen presentation capacity of murine macrophages infected with Leishmania amazonensis amastigotes","volume":"151","author":"Prina","year":"1993","journal-title":"J. Immunol."},{"key":"2025032404355616600_r25","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1084\/jem.185.8.1403","article-title":"Enhanced intracellular dissociation of major histocompatibility complex class I-associated peptides: a mechanism for optimizing the spectrum of cell surface-presented cytotoxic T lymphocyte epitopes","volume":"185","author":"Sijts","year":"1997","journal-title":"J. Exp. Med."},{"key":"2025032404355616600_r26","doi-asserted-by":"crossref","first-page":"2480","DOI":"10.1172\/JCI44932","article-title":"Variable HIV peptide stability in human cytosol is critical to epitope presentation and immune escape","volume":"121","author":"Lazaro","year":"2011","journal-title":"J. Clin. Invest."},{"key":"2025032404355616600_r27","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0764-4469(97)89621-7","article-title":"An accessory peptide binding site with allosteric effect on the formation of peptide-MHC-II complexes?","volume":"321","author":"Gerlier","year":"1998","journal-title":"C. R. Acad. Sci. III"},{"key":"2025032404355616600_r28","doi-asserted-by":"crossref","first-page":"573","DOI":"10.4049\/jimmunol.0902107","article-title":"Peptide-MHC class II complex stability governs CD4 T cell clonal selection","volume":"184","author":"Baumgartner","year":"2010","journal-title":"J. Immunol."},{"key":"2025032404355616600_r29","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1146\/annurev.immunol.15.1.297","article-title":"Induction of Th1 and Th2 CD4+ T cell responses: the alternative approaches","volume":"15","author":"Constant","year":"1997","journal-title":"Annu. Rev. Immunol."},{"key":"2025032404355616600_r30","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.immuni.2005.05.009","article-title":"The kinetic stability of MHC class II:peptide complexes is a key parameter that dictates immunodominance","volume":"23","author":"Lazarski","year":"2005","journal-title":"Immunity"},{"key":"2025032404355616600_r31","doi-asserted-by":"crossref","first-page":"4682","DOI":"10.1016\/j.vaccine.2013.06.110","article-title":"Carrier protein influences immunodominance of a known epitope: implication in peptide vaccine design","volume":"31","author":"Ghosh","year":"2013","journal-title":"Vaccine"},{"key":"2025032404355616600_r32","doi-asserted-by":"crossref","first-page":"e1000907","DOI":"10.1371\/journal.ppat.1000907","article-title":"Leishmania donovani isolates with antimony-resistant but not -sensitive phenotype inhibit sodium antimony gluconate-induced dendritic cell activation","volume":"6","author":"Haldar","year":"2010","journal-title":"PLoS Pathog."},{"key":"2025032404355616600_r33","doi-asserted-by":"crossref","first-page":"3214","DOI":"10.4049\/jimmunol.175.5.3214","article-title":"Leishmania donovani affects antigen presentation of macrophage by disrupting lipid rafts","volume":"175","author":"Chakraborty","year":"2005","journal-title":"J. Immunol."},{"key":"2025032404355616600_r34","doi-asserted-by":"crossref","first-page":"3106","DOI":"10.1194\/jlr.M041954","article-title":"Cholesterol lowering drug may influence cellular immune response by altering MHC II function","volume":"54","author":"Roy","year":"2013","journal-title":"J. Lipid Res."},{"key":"2025032404355616600_r35","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1016\/j.ab.2009.09.049","article-title":"Surface plasmon resonance analysis of ricin binding to plasma membranes isolated from NIH 3T3 cells","volume":"396","author":"Blome","year":"2010","journal-title":"Anal. Biochem."},{"key":"2025032404355616600_r36","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1023\/B:PHAM.0000012152.86004.aa","article-title":"Preparation and characterization of reconstructed small intestinal brush border membranes for surface plasmon resonance analysis","volume":"21","author":"Cho","year":"2004","journal-title":"Pharm. Res."},{"key":"2025032404355616600_r37","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1007\/s10571-007-9138-0","article-title":"Membrane organization of the serotonin 1A receptor monitored by a detergent-free approach","volume":"27","author":"Kalipatnapu","year":"2007","journal-title":"Cell. Mol. Neurobiol."},{"key":"2025032404355616600_r38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0022-1759(90)90107-7","article-title":"Detection of peptide-MHC class II complexes on the surface of intact cells","volume":"134","author":"Busch","year":"1990","journal-title":"J. Immunol. Methods"},{"key":"2025032404355616600_r39"},{"key":"2025032404355616600_r40","doi-asserted-by":"crossref","first-page":"6680","DOI":"10.4049\/jimmunol.166.11.6680","article-title":"Peptide binding to active class II MHC protein on the cell surface","volume":"166","author":"Vacchino","year":"2001","journal-title":"J. Immunol."},{"key":"2025032404355616600_r41","doi-asserted-by":"crossref","first-page":"38535","DOI":"10.1074\/jbc.M606437200","article-title":"Small organic compounds enhance antigen loading of class II major histocompatibility complex proteins by targeting the polymorphic P1 pocket","volume":"281","author":"H\u00f6pner","year":"2006","journal-title":"J. Biol. Chem."},{"key":"2025032404355616600_r42","doi-asserted-by":"crossref","first-page":"6647","DOI":"10.1073\/pnas.82.19.6647","article-title":"Analysis of antigen presentation by metabolically inactive accessory cells and their isolated membranes","volume":"82","author":"Falo","year":"1985","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2025032404355616600_r43","doi-asserted-by":"crossref","first-page":"420","DOI":"10.4049\/jimmunol.143.2.420","article-title":"Stable association of processed antigen with antigen-presenting cell membranes","volume":"143","author":"Jensen","year":"1989","journal-title":"J. Immunol."},{"key":"2025032404355616600_r44","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1093\/intimm\/2.5.443","article-title":"Degenerate binding of immunogenic peptides to HLA-DR proteins on B cell surfaces","volume":"2","author":"Busch","year":"1990","journal-title":"Int. Immunol."},{"key":"2025032404355616600_r45","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1126\/science.2470147","article-title":"Murine MHC polymorphism and T cell specificities","volume":"244","author":"Roy","year":"1989","journal-title":"Science"},{"key":"2025032404355616600_r46","doi-asserted-by":"crossref","first-page":"54002","DOI":"10.1074\/jbc.M403909200","article-title":"T cell antigen receptor peptide-lipid membrane interactions using surface plasmon resonance","volume":"279","author":"Bender","year":"2004","journal-title":"J. Biol. Chem."},{"key":"2025032404355616600_r47","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1093\/intimm\/4.8.889","article-title":"Conformational changes in mouse MHC class II proteins at acidic pH","volume":"4","author":"Lee","year":"1992","journal-title":"Int. Immunol."},{"key":"2025032404355616600_r48","doi-asserted-by":"crossref","first-page":"2614","DOI":"10.1128\/iai.62.6.2614-2618.1994","article-title":"Leishmania-reactive CD4+ and CD8+ T cells associated with cure of human cutaneous leishmaniasis","volume":"62","author":"Da-Cruz","year":"1994","journal-title":"Infect. Immun."},{"key":"2025032404355616600_r49","doi-asserted-by":"crossref","first-page":"3153","DOI":"10.1002\/eji.1830261248","article-title":"Antigen presentation by Leishmania mexicana-infected macrophages: activation of helper T cells by a model parasite antigen secreted into the parasitophorous vacuole or expressed on the amastigote surface","volume":"26","author":"Wolfram","year":"1996","journal-title":"Eur. J. Immunol."},{"key":"2025032404355616600_r50","doi-asserted-by":"crossref","first-page":"5346","DOI":"10.4049\/jimmunol.172.9.5346","article-title":"The magnitude of TCR engagement is a critical predictor of T cell anergy or activation","volume":"172","author":"Mirshahidi","year":"2004","journal-title":"J. Immunol."},{"key":"2025032404355616600_r51","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1038\/jid.2009.393","article-title":"Enhanced lesional Foxp3 expression and peripheral anergic lymphocytes indicate a role for regulatory T cells in Indian post-kala-azar dermal leishmaniasis","volume":"130","author":"Ganguly","year":"2010","journal-title":"J. Invest. Dermatol."},{"key":"2025032404355616600_r52","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1007\/s10495-006-0088-7","article-title":"Lymph node cells from BALB\/c mice with chronic visceral leishmaniasis exhibiting cellular anergy and apoptosis: involvement of Ser\/Thr phosphatase","volume":"11","author":"Mukherjee","year":"2006","journal-title":"Apoptosis"},{"key":"2025032404355616600_r53","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1016\/S0966-842X(98)01324-9","article-title":"The biogenesis and properties of the parasitophorous vacuoles that harbour Leishmania in murine macrophages","volume":"6","author":"Antoine","year":"1998","journal-title":"Trends Microbiol."},{"key":"2025032404355616600_r54","doi-asserted-by":"crossref","first-page":"609","DOI":"10.4049\/jimmunol.152.2.609","article-title":"Kinetics and specificity of peptide-MHC class II complex displacement reactions","volume":"152","author":"de Kroon","year":"1994","journal-title":"J. Immunol."},{"key":"2025032404355616600_r55","doi-asserted-by":"crossref","first-page":"e6811","DOI":"10.1371\/journal.pone.0006811","article-title":"Enhancement of tumour-specific immune responses in vivo by \u2018MHC loading-enhancer\u2019 (MLE)","volume":"4","author":"Dickhaut","year":"2009","journal-title":"PLoS ONE"},{"key":"2025032404355616600_r56","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1128\/IAI.00057-09","article-title":"Designing therapies against experimental visceral leishmaniasis by modulating the membrane fluidity of antigen-presenting cells","volume":"77","author":"Banerjee","year":"2009","journal-title":"Infect. Immun."},{"key":"2025032404355616600_r57","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.vaccine.2012.12.013","article-title":"High-dose trivalent influenza vaccine compared to standard dose vaccine in elderly adults: safety, immunogenicity and relative efficacy during the 2009-2010 season","volume":"31","author":"DiazGranados","year":"2013","journal-title":"Vaccine"}],"container-title":["The Journal of Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/192\/12\/5873\/61762020\/1302970.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jimmunol\/article-pdf\/192\/12\/5873\/61762020\/1302970.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T15:33:28Z","timestamp":1742830408000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jimmunol\/article\/192\/12\/5873\/8001751"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,6]]},"references-count":57,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2014,6,15]]}},"URL":"https:\/\/doi.org\/10.4049\/jimmunol.1302970","relation":{},"ISSN":["0022-1767","1550-6606"],"issn-type":[{"value":"0022-1767","type":"print"},{"value":"1550-6606","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2014,6]]},"published":{"date-parts":[[2014,6]]}}}