Allorecognition, Transplant Rejection & GvHD
A transplanted graft is rejected because its MHC is not yours. Recipient T cells reach that conclusion by three different routes. In direct allorecognition the TCR reads intact donor MHC class I — H-2Kb, H-2Db, H-2Kd in mouse models, HLA-A/B/C in human — on donor passenger leukocytes. In indirect allorecognition, recipient antigen-presenting cells process shed donor MHC and re-present the peptides on their own class II to CD4 T cells. In the semi-direct route, whole donor MHC molecules are transferred by exosome or trogocytosis and the recipient APC is cross-dressed. All three converge on the same synapse — CD80/CD86–CD28, CD40–CD40L, ICAM-1–LFA-1 — and split into a cellular arm (perforin, granzyme B, FasL), a humoral arm (donor-specific antibody, C1q, C4, C4d, C5) and, if the balance holds, a FoxP3 regulatory arm. Meanwhile NK cells read the absence of self MHC through Ly49C and NKG2A. Click any protein for the matching Assay Genie In Vivo antibody or ELISA kit.
Three routes, one rejection. Direct allorecognition is the reason transplant rejection is so much faster and so much more violent than a normal antigen response: an unusually large fraction of the recipient's naive T-cell repertoire — often quoted at 1–10% — cross-reacts with intact allogeneic MHC on donor passenger leukocytes, without any processing step. It dominates early acute rejection and it fades as donor leukocytes are lost. Indirect allorecognition is slower and does not fade: recipient APCs take up shed donor MHC, process it, and present allopeptides on self class II to CD4 T cells — this is the arm that sustains chronic rejection and supplies help to alloreactive B cells. The semi-direct route sits between the two: intact donor MHC–peptide complexes are transferred to recipient APCs on exosomes or by trogocytosis, so one recipient APC can prime a direct-pathway CD8 cell and an indirect-pathway CD4 cell at the same time. In graft-versus-host disease the geometry is inverted — donor T cells in the graft read recipient MHC — but the molecular grammar on this map is unchanged.
The synapse and the missing-self counterpart. Alloreactive T cells still need the same second signal as any other T cell: CD80 and CD86 engaging CD28, CD40L engaging CD40 on the APC, and LFA-1 holding on to ICAM-1 long enough for the synapse to mature; CTLA-4 is the counterweight, and co-stimulation blockade is built on exactly that asymmetry. NK cells work by the opposite logic. Ly49C and NKG2A/C/E are inhibited by self MHC class I, so a graft that mismatches or downregulates MHC loses that inhibition and becomes an NK target — missing-self recognition, and the reason KIR/Ly49 mismatch matters in haematopoietic transplant.
Cellular, humoral, or tolerant. The cellular arm ends in CTL and NK killing of graft parenchyma through perforin, granzyme B and FasL, amplified by IFN-γ and the CXCL9 it induces. The humoral arm runs through indirect CD4 help to alloreactive B cells (CD20), to plasma cells (CD38) and to donor-specific antibody, which fixes C1q and cleaves C4 — leaving C4d covalently bound to graft endothelium, the biopsy marker that defines antibody-mediated rejection — before C3 and C5 complete the cascade. The third outcome is tolerance: IL-2 captured through high-affinity CD25 sustains FoxP3 regulatory T cells, which is why low-dose IL-2 and anti-CD25 pull in opposite directions and why timing matters more than potency.
The In Vivo tie-in. This is the deepest In Vivo cluster Assay Genie stocks, and the map doubles as the intervention plan. Induction depletion: anti-CD4 (GK1.5), anti-CD8α, anti-CD90/Thy-1, anti-NK1.1, and the anti-CD52 alemtuzumab biosimilar. Antigen-side blockade: low-endotoxin antibodies against H-2Kb, H-2Db, H-2Kd, H-2b, HLA-A/B/C, HLA-A2/B7, HLA-DR, HLA-DQ and HLA-DP. Co-stimulation blockade: CD80, CD86, CD28, CTLA-4, CD40. Adhesion blockade: CD11a/LFA-1, ICAM-1, CD62L. Cytokine and complement: anti-IL-2, anti-CD25, and the anti-C5 eculizumab biosimilar for the humoral arm. Rodent models also need the anti-rat κ light chain antibody to track donor-specific antibody itself. For research use only; not for use in diagnostic or therapeutic procedures.
Every protein node links to a product — In Vivo antibody, ELISA kit or research antibody.