Immunization with mannosylated peptide induces poor T cell effector functions despite enhanced antigen presentation.
In this study, we investigated the development of T cell responses in mice after administration of a mannosylated ovalbumin peptide (M-OVA(323-339)). Immunization with M-OVA(323-339) in complete adjuvant resulted in enhanced antigen presentation in draining lymph nodes. Monitoring the fate of CFSE-labeled ovalbumin peptide-specific TCR transgenic CD4(+) T cells revealed that immunization with M-OVA(323-339) induced normal clonal expansion, recirculation and CD62L expression of antigen-specific T cells in vivo. However, these T cells developed only poor effector functions, reflected by minimal IFN-gamma production, low IgG2a levels in serum and poor peptide-specific delayed-type hypersensitivity (DTH) responses. This diminished inflammatory response was associated with decreased infiltration of T cell blasts and macrophages. Importantly, also mice with functional effector T cells did not mount a robust DTH response after a challenge with M-OVA(323-339) in the ear, although their T cells responded normally to M-OVA(323-339) in vitro. In conclusion, mannosylated peptide induces proliferation of T cells with impaired T(h)1 cell effector functions and additionally abrogates the activity of pre-existing effector T cells.
Kel
Junda M
JM
Business Unit Biosciences, TNO Quality of Life, Zernikedreef 9, 2333 CK Leiden, The Netherlands. j.m.kel@amc.uva.nl
de Geus
Eveline D
ED
van Stipdonk
Marianne J
MJ
Drijfhout
Jan W
JW
Koning
Frits
F
Nagelkerken
Lex
L
D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation; D005260:Female; D006968:Hypersensitivity, Delayed; D007114:Immunization; D008213:Lymphocyte Activation; D008358:Mannose / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010047:Ovalbumin / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology*
D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin; D008358:Mannose