title: A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8(+) T Cells.
abstract: The most effective strategy for protection against intracellular infections such as Leishmania is vaccination with live parasites. Use of recombinant proteins avoids the risks associated with live vaccines. However, due to low immunogenicity, they fail to trigger T cell responses particularly of CD8(+) cells requisite for persistent immunity. Previously we showed the importance of protein entrapment in cationic liposomes and MPL as adjuvant for elicitation of CD4(+) and CD8(+) T cell responses for long-term protection. In this study we investigated the role of cationic liposomes on maturation and antigen presentation capacity of dendritic cells (DCs). We observed that cationic liposomes were taken up very efficiently by DCs and transported to different cellular sites. DCs activated with liposomal rgp63 led to efficient presentation of antigen to specific CD4(+) and CD8(+) T cells. Furthermore, lymphoid CD8(+) T cells from liposomal rgp63 immunized mice demonstrated better proliferative ability when co-cultured ex vivo with stimulated DCs. Addition of MPL to vaccine enhanced the antigen presentation by DCs and induced more efficient antigen specific CD8(+) T cell responses when compared to free and liposomal antigen. These liposomal formulations presented to CD8(+) T cells through TAP-dependent MHC-I pathway offer new possibilities for a safe subunit vaccine.
authors.affiliation: Indian Institute of Chemical Biology, Infectious Diseases and Immunology Division, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata-700032, India.
authors.forename: Mithun
authors.initials: M
authors.lastname: Maji
authors.affiliation: Indian Institute of Chemical Biology, Infectious Diseases and Immunology Division, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata-700032, India.
authors.forename: Saumyabrata
authors.initials: S
authors.lastname: Mazumder
authors.affiliation: Indian Institute of Chemical Biology, Infectious Diseases and Immunology Division, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata-700032, India.
authors.forename: Souparno
authors.initials: S
authors.lastname: Bhattacharya
authors.affiliation: Indian Institute of Chemical Biology, Infectious Diseases and Immunology Division, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata-700032, India.
authors.forename: Somsubhra Thakur
authors.initials: ST
authors.lastname: Choudhury
authors.affiliation: Indian Institute of Chemical Biology, Infectious Diseases and Immunology Division, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata-700032, India.
authors.forename: Abdus
authors.initials: A
authors.lastname: Sabur
authors.affiliation: Indian Institute of Chemical Biology, Infectious Diseases and Immunology Division, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata-700032, India.
authors.forename: Md
authors.initials: M
authors.lastname: Shadab
authors.affiliation: Indian Institute of Chemical Biology, Infectious Diseases and Immunology Division, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata-700032, India.
authors.forename: Pradyot
authors.initials: P
authors.lastname: Bhattacharya
authors.affiliation: Indian Institute of Chemical Biology, Infectious Diseases and Immunology Division, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata-700032, India.
authors.forename: Nahid
authors.initials: N
authors.lastname: Ali
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D017951:Antigen Presentation; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005260:Female; D015395:Histocompatibility Antigens Class I / Q000378:metabolism*; D007114:Immunization; D008081:Liposomes / Q000008:administration & dosage* / Q000494:pharmacology; D008666:Metalloendopeptidases / Q000008:administration & dosage / Q000276:immunology; D051379:Mice; D011994:Recombinant Proteins / Q000008:administration & dosage* / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D015395:Histocompatibility Antigens Class I; D008081:Liposomes; D011994:Recombinant Proteins; D008666:Metalloendopeptidases; C055146:glycoprotein gp63, Leishmania