SEARCH

SEARCH BY CITATION

Additional Supporting Information may be found in the online version of this article.

FilenameFormatSizeDescription
ajt12432-sup-0001-SuppFig-S1.pdf200K

Figure S1: Schematic representation of cognate help provided by HY-reactive Mar T cells for donor MHC-reactive B cells. After placement of male allogeneic heart transplants into C57BL/6 (B6, H-2b) female recipients, transferred Mar T cells recognize donor male antigen presented by female antigen-presenting cells through the indirect pathway. Along with dendritic cells, recipient B cells may also serve as antigen-presenting cells and present donor antigens through the indirect pathway [32-34]. According to the principle of linked epitope recognition, B cells are up to 10 000 times more likely to present peptides that are physically connected to the epitopes recognized by B cell responses [35]. After transplantation, B cells recognizing MHC and other surface molecules on donor cells process and present various intra- and extracellular peptides from donor cells including HY antigens to helper CD4 T cells and thus receive cognate help. Importantly, the B cells receiving help are not specific for HY antigens, but recognize donor MHC among other epitopes eventually leading to production of antibodies against donor MHC molecules.

Figure S2: Polyclonal donor-reactive memory CD4 T cells induce IgG alloantibody responses in CD40−/− heart allograft recipients. CD40−/− mice were injected with 5 × 106 naïve (circles) or C3H-reactive memory (squares) CD4 T cells generated as outlined in the Materials and Methods section and transplanted with C3H heart allografts. Control CD40−/− female recipients of C3H male heart allografts did not receive Mar cells (triangles). Serum titers of donor or third-party BALB/c-reactive IgG alloantibody were determined on Day 14 posttransplant. The titers of third-party-reactive Ab were ≤135 for all IgG isotypes in all groups.

Figure S3: TCR transgenic but not polyclonal donor-reactive memory CD4 T cells provide help independent of CD154 and ICOS. CD40−/− female mice containing either polyclonal memory CD4 T cells (A) or Mar memory T cells (B) were transplanted with C3H heart allografts and treated with anti-ICOS mAb on Days 0, 2, 4, 6, 8 and 10 after transplantation. Serum titers of donor or third-party BALB/c-reactive IgG alloantibody were determined on Day 14 posttransplant. The titers of third-party-reactive Ab were ≤135 for all IgG isotypes in (A) and ≤45 in (B). The experiment in (B) was performed three times with similar results.

Please note: Wiley Blackwell is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.