This pathway illustrates molecular interactions involved in the fundamental adaptive immune response for allograft destruction. This pathway was adapted in large part from [http://www.genome.jp/kegg/pathway/hsa/hsa05330.html KEGG]. In the initial step of this diagram, antigen presenting cells (APC's), either those from the donor (direct pathway) or from the recipient (indirect pathway) activate naive t cells leading to both CD8+ and CD4+ T cell maturation. CD8+ stimulated T cells lead to apoptosis of the allograft donor cells whereas CD4+ T cells differentiate into TH1, TH2, T17, and Treg cells. Activated TH1 produces TNFA and NO and damages donor graft cells by cytotoxicity. TH2 cell activates B cells. Activated B cells lead to plasma cell formation followed by IgG antibodies and the complement cascade pathway in acute antibody-mediated rejection (AMR) and chronic AMR with C3 being the therapeutic target. Exogenous treatment with YCF inhibits C3, thus preventing AMR. Eculizumab binds to C5 which prevent C5a production and the membrane attack complex. C3a and C35 act as potent chemotactic factors, promoting the infiltration of pro-inflammatory cells. Belatacept inhibits CD80/86 binding to CD28. Corticosteroids inhibit pro-inflammatory cytokines. Corticosteroids contribute to immune suppression such as CTLA4 which inhibits T-cell activation. Proteins on this pathway have targeted assays available via the [https://assays.cancer.gov/available_assays?wp_id=WP2328 CPTAC Assay Portal] f48 bde d87 bb2 e98 cbe f4e fac Original kegg element: gene;29;hsa:940 Original kegg element: gene;41;hsa:3592 hsa:3593 Original kegg element: gene;20;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 previously: ko:K10785 ; T-cell receptor beta chain V region Original kegg element: gene;31;hsa:3586 Original kegg element: map;7;path:hsa04514 Original kegg element: gene;20;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 Original kegg element: gene;20;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 Original kegg element: gene;22;hsa:5551 Original kegg element: gene;20;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 Original kegg element: gene;20;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 Original kegg element: gene;21;hsa:3002 Original kegg element: gene;39;hsa:7124 Previously: ko:K10784 ; T cell receptor alpha chain V region Original kegg element: gene;27;hsa:3567 Original kegg element: gene;26;hsa:3565 Original kegg element: gene;41;hsa:3592 hsa:3593 Original kegg element: gene;34;hsa:3458 Original kegg element: gene;38;hsa:959 Original kegg element: gene;37;hsa:958 Original kegg element: gene;17;hsa:355 Original kegg element: gene;20;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 Original kegg element: gene;18;hsa:356 Original kegg element: gene;20;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 Previously: ko:K06856 update: C1QA HUMAN update C1QC HUMAN Original kegg element: gene;38;hsa:959 Original kegg element: gene;37;hsa:958 Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 Original kegg element: gene;28;hsa:941 hsa:942 Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 Original kegg element: gene;10;hsa:100133583 hsa:3108 hsa:3109 hsa:3111 hsa:3112 hsa:3113 hsa:3115 hsa:3117 hsa:3118 hsa:3119 hsa:3122 hsa:3123 hsa:3125 hsa:3126 hsa:3127 Original kegg element: gene;36;hsa:940 Original kegg element: gene;35;hsa:941 hsa:942 Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 Original kegg element: gene;32;hsa:3105 hsa:3106 hsa:3107 hsa:3133 hsa:3134 hsa:3135 hsa:652614 Original kegg element: gene;35;hsa:941 hsa:942 f22 f22 PPrel;18;17 activation; --> PPrel;35;36 activation; --> PPrel;32;33 activation; --> PPrel;38;37 activation; --> PPrel;20;19 activation; --> PPrel;28;29 activation; --> PPrel;10;11 activation; --> PPrel;38;37 activation; --> allograft rejection pathway PW:0001025 Pathway Ontology disease pathway PW:0000013 Pathway Ontology adaptive immune response pathway PW:0000235 Pathway Ontology 20925547 PubMed Rejection of the kidney allograft. N Engl J Med 2010 Nankivell BJ Alexander SI 22302197 PubMed Non-HLA antibodies to immunogenic epitopes predict the evolution of chronic renal allograft injury. J Am Soc Nephrol 2012 Sigdel TK Li L Tran TQ Khatri P Naesens M Sansanwal P Dai H Hsieh SC Sarwal MM 22678861 PubMed Transplant immunology for non-immunologist. Mt Sinai J Med 2012 Heeger PS Dinavahi R 22790079 PubMed Role of non-HLA antibodies in organ transplantation. Curr Opin Organ Transplant 2012 Dragun D Philippe A Catar R 23026942 PubMed The role of complement in antibody-mediated rejection in kidney transplantation. Nat Rev Nephrol 2012 Stegall MD Chedid MF Cornell LD 12581329 PubMed Increased expression of cytotoxic effector molecules: different interpretations for steroid-based and steroid-free immunosuppression. Pediatr Transplant 2003 Satterwhite T Chua MS Hsieh SC Chang S Scandling J Salvatierra O Sarwal MM 18547992 PubMed Characterization of intra-graft B cells during renal allograft rejection. Kidney Int 2008 Zarkhin V Kambham N Li L Kwok S Hsieh SC Salvatierra O Sarwal MM 19857756 PubMed Balancing efficacy and toxicity of kidney transplant immunosuppression. Transplant Proc 2009 Naesens M Lerut E Sarwal M Van Damme B Vanrenterghem Y Kuypers DR 23437201 PubMed Significance and suppression of redundant IL17 responses in acute allograft rejection by bioinformatics based drug repositioning of fenofibrate. PLoS One 2013 Roedder S Kimura N Okamura H Hsieh SC Gong Y Sarwal MM