Premium
Novel function of complement C3d as an autologous helper T cell target
Author(s) -
Knopf Paul,
Hai SiHan,
Rivera Daniel S.,
Martin William,
McMurray Julie,
De Groot Anne S.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.673.5
Subject(s) - epitope , t cell , microbiology and biotechnology , antigen presenting cell , immune system , biology , b cell , adjuvant , complement system , antigen , immunology , antibody
The C3d fragment of complement component C3 has been shown to enhance immune responses to antigens that lack T‐cell epitopes such as bacterial polysaccharides by binding to the B cell complement receptor (CD21). Paradoxically, C3d has also been shown to enhance B cell and T cell responses in the CD21 KO mouse model, suggesting that that an auxiliary CR2‐independent pathway of immune activation may exist. We hypothesized that in addition to its molecular adjuvant property that enhances signal 1 during B cell activation (co‐signal 1), C3d also contains T cell epitopes that are able to stimulate autoreactive C3d peptide‐specific helper T cells which we term “co‐signal 2”. Using the EpiMatrix T‐cell epitope‐mapping algorithm, we identified 11 putative T‐cell epitopes in C3d. Stimulation of human PBMC with C3d‐derived peptides leads to dramatic increases IFN‐γ secretion. These IFN‐γ secreting cells were exclusively found to reside in the CD4+ T helper subset by FACS analysis. We believe that the discovery of these autologous T cells autoreactive for C3d provides evidence supporting the “co‐signal 2” hypothesis and may offer a novel explanation of the CD21 KO paradox. This data suggests a novel mechanism for the adjuvant effect of C3d and raises questions regarding self‐tolerance and suggests the possibility of AIRE‐independent differentiation into non‐pathogenic, self‐reactive T cells. All work funded by EpiVax, Inc.