KEGG   PATHWAY: hsa05330
Entry
hsa05330                    Pathway                                
Name
Allograft rejection - Homo sapiens (human)
Description
Allograft rejection is the consequence of the recipient's alloimmune response to nonself antigens expressed by donor tissues. After transplantation of organ allografts, there are two pathways of antigen presentation. In the direct pathway, recipient T cells react to intact allogeneic MHC molecules expressed on the surface of donor cells. This pathway would activate host CD4 or CD8 T cells. In contrast, donor MHC molecules (and all other proteins) shed from the graft can be taken up by host APCs and presented to recipient T cells in the context of self-MHC molecules - the indirect pathway. Such presentation activates predominantly CD4 T cells. A direct cytotoxic T-cell attack on graft cells can be made only by T cells that recognize the graft MHC molecules directly. Nontheless, T cells with indirect allospecificity can contribute to graft rejection by activating macrophages, which cause tissue injury and fibrosis, and are also likely to be important in the development of an alloantibody response to graft.
Class
Human Diseases; Immune disease
Pathway map
hsa05330  Allograft rejection
hsa05330

Disease
H00083  Allograft rejection
Drug
D03222  Belatacept (USAN/INN)
D06071  Teneliximab (USAN/INN)
D11357  Bleselumab (USAN/INN)
D11610  Iscalimab (USAN/INN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
3105  HLA-A; major histocompatibility complex, class I, A [KO:K06751]
3106  HLA-B; major histocompatibility complex, class I, B [KO:K06751]
3107  HLA-C; major histocompatibility complex, class I, C [KO:K06751]
3134  HLA-F; major histocompatibility complex, class I, F [KO:K06751]
3135  HLA-G; major histocompatibility complex, class I, G [KO:K06751]
3133  HLA-E; major histocompatibility complex, class I, E [KO:K06751]
941  CD80; CD80 molecule [KO:K05412]
942  CD86; CD86 molecule [KO:K05413]
940  CD28; CD28 molecule [KO:K06470]
3592  IL12A; interleukin 12A [KO:K05406]
3593  IL12B; interleukin 12B [KO:K05425]
356  FASLG; Fas ligand [KO:K04389]
355  FAS; Fas cell surface death receptor [KO:K04390]
5551  PRF1; perforin 1 [KO:K07818]
3002  GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]
3108  HLA-DMA; major histocompatibility complex, class II, DM alpha [KO:K06752]
3109  HLA-DMB; major histocompatibility complex, class II, DM beta [KO:K06752]
3111  HLA-DOA; major histocompatibility complex, class II, DO alpha [KO:K06752]
3112  HLA-DOB; major histocompatibility complex, class II, DO beta [KO:K06752]
3113  HLA-DPA1; major histocompatibility complex, class II, DP alpha 1 [KO:K06752]
3115  HLA-DPB1; major histocompatibility complex, class II, DP beta 1 [KO:K06752]
3117  HLA-DQA1; major histocompatibility complex, class II, DQ alpha 1 [KO:K06752]
3118  HLA-DQA2; major histocompatibility complex, class II, DQ alpha 2 [KO:K06752]
3119  HLA-DQB1; major histocompatibility complex, class II, DQ beta 1 [KO:K06752]
3122  HLA-DRA; major histocompatibility complex, class II, DR alpha [KO:K06752]
3123  HLA-DRB1; major histocompatibility complex, class II, DR beta 1 [KO:K06752]
3125  HLA-DRB3; major histocompatibility complex, class II, DR beta 3 [KO:K06752]
3126  HLA-DRB4; major histocompatibility complex, class II, DR beta 4 [KO:K06752]
3127  HLA-DRB5; major histocompatibility complex, class II, DR beta 5 [KO:K06752]
3558  IL2; interleukin 2 [KO:K05429]
959  CD40LG; CD40 ligand [KO:K03161]
958  CD40; CD40 molecule [KO:K03160]
3458  IFNG; interferon gamma [KO:K04687]
7124  TNF; tumor necrosis factor [KO:K03156]
3565  IL4; interleukin 4 [KO:K05430]
3567  IL5; interleukin 5 [KO:K05428]
3586  IL10; interleukin 10 [KO:K05443]
102723407  IGH; immunoglobulin heavy variable 4-38-2-like [KO:K06856]
Compound
C00533  Nitric oxide
Reference
  Authors
Arakelov A, Lakkis FG.
  Title
The alloimmune response and effector mechanisms of allograft rejection.
  Journal
Semin Nephrol 20:95-102 (2000)
Reference
  Authors
Le Moine A, Goldman M, Abramowicz D.
  Title
Multiple pathways to allograft rejection.
  Journal
Transplantation 73:1373-81 (2002)
DOI:10.1097/00007890-200205150-00001
Reference
  Authors
Trivedi HL.
  Title
Immunobiology of rejection and adaptation.
  Journal
Transplant Proc 39:647-52 (2007)
DOI:10.1016/j.transproceed.2007.01.047
Reference
  Authors
Pietra BA.
  Title
Transplantation immunology 2003: simplified approach.
  Journal
Pediatr Clin North Am 50:1233-59 (2003)
DOI:10.1016/S0031-3955(03)00119-6
Reference
PMID:8835634
  Authors
Oka T, Yoshimura N.
  Title
Immunosuppression in organ transplantation.
  Journal
Jpn J Pharmacol 71:89-100 (1996)
DOI:10.1254/jjp.71.89
Reference
  Authors
Sayegh MH.
  Title
Why do we reject a graft? Role of indirect allorecognition in graft rejection.
  Journal
Kidney Int 56:1967-79 (1999)
DOI:10.1046/j.1523-1755.1999.00751.x
Reference
  Authors
Benichou G.
  Title
Direct and indirect antigen recognition: the pathways to allograft immune rejection.
  Journal
Front Biosci 4:D476-80 (1999)
DOI:10.2741/benichou
Reference
  Authors
Turvey SE, Wood KJ.
  Title
Immunobiology of solid organ transplantation.
  Journal
Int Surg 84:279-90 (1999)
Reference
  Authors
Janeway CA, Travers P, Walport M, Shlomchik MJ.
  Title
Immunobiology 6th edition
  Journal
Garland Science Publishing (2005)
Reference
  Authors
Game DS, Lechler RI.
  Title
Pathways of allorecognition: implications for transplantation tolerance.
  Journal
Transpl Immunol 10:101-8 (2002)
DOI:10.1016/S0966-3274(02)00055-2
Reference
  Authors
Lechler RI, Garden OA, Turka LA.
  Title
The complementary roles of deletion and regulation in transplantation tolerance.
  Journal
Nat Rev Immunol 3:147-58 (2003)
DOI:10.1038/nri1002
Related
pathway
hsa04210  Apoptosis
hsa04514  Cell adhesion molecules
hsa04610  Complement and coagulation cascades
hsa04612  Antigen processing and presentation
hsa04660  T cell receptor signaling pathway
hsa04662  B cell receptor signaling pathway
KO pathway
ko05330   

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