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
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   PMID:10746853
  AUTHORS   Arakelov A, Lakkis FG.
  TITLE     The alloimmune response and effector mechanisms of allograft rejection.
  JOURNAL   Semin Nephrol 20:95-102 (2000)
REFERENCE   PMID:12023610
  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   PMID:17445565
  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   PMID:14710779
  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   PMID:10571983
  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   PMID:10331992
  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   PMID:10667806
  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   PMID:12216939
  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   PMID:12563298
  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
REL_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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