Transplant Immunology and Immunosuppression: Core Curriculum 2015 Donald E. Hricik, MD  American Journal of Kidney Diseases  Volume 65, Issue 6, Pages 956-966 (June 2015) DOI: 10.1053/j.ajkd.2015.01.026 Copyright © 2015 National Kidney Foundation, Inc. Terms and Conditions

Figure 1 Schematic of the peptide-binding pockets for class II molecules derived from the DP, DQ, or DR loci of the major histocompatibility complex of chromosome 6 and for class I molecules derived from the B, C, or A loci. Figure courtesy of Dr P. Heeger; adapted from Schröppel and Heeger (Transplantation Immunology. In: Hricik DE, ed. Kidney Transplantation. 2nd ed. London: Remedica, 2007:9-38) with permission of Remedica Medical Education and Publishing. American Journal of Kidney Diseases 2015 65, 956-966DOI: (10.1053/j.ajkd.2015.01.026) Copyright © 2015 National Kidney Foundation, Inc. Terms and Conditions

Figure 2 (A) Depiction of direct allorecognition in which a donor antigen-presenting cell (APC) presents peptide to the T-cell receptor (TCR) within the context of donor major histocompatibility complex (MHC) molecule. (Left side) Presentation of a peptide within a class I MHC molecule to a CD8-positive T cell. (Right side) Presentation of a peptide within a class II MHC molecule to a CD4-positive T cell. (B) Depiction of indirect allorecognition in which an antigen is first processed by a recipient APC and then presented within the context of a recipient MHC molecule to either a CD4- or CD8-positive T cell. Figure courtesy of P. Heeger. American Journal of Kidney Diseases 2015 65, 956-966DOI: (10.1053/j.ajkd.2015.01.026) Copyright © 2015 National Kidney Foundation, Inc. Terms and Conditions

Figure 3 Depiction of 2 costimulatory signals, CD40:CD40 ligand (CD40L) and B7:CD28, which are required for full T-cell activation, beginning with presentation of a peptide by an antigen-presenting cell (APC) to the T-cell receptor (TCR). The B7 accessory molecule consists of either CD80 or CD86, which binds to CD28 with different affinities. Abbreviation: MHC, major histocompatibility complex. Figure courtesy of P. Heeger. American Journal of Kidney Diseases 2015 65, 956-966DOI: (10.1053/j.ajkd.2015.01.026) Copyright © 2015 National Kidney Foundation, Inc. Terms and Conditions

Figure 4 Schematic of the 3 signals required for full activation and proliferation of T cells and the sites of action for commonly used maintenance immunosuppressive drugs. See text for details. Abbreviations: IL-2R, interleukin 2 receptor; MPA, mycophenolic acid; TCR, T cell receptor; TOR, target of rapamycin. Figure courtesy of P. Heeger; adapted from Schröppel and Heeger (Transplantation Immunology. In: Hricik DE, ed. Kidney Transplantation. 2nd ed. London: Remedica, 2007:9-38) with permission of Remedica Medical Education and Publishing. American Journal of Kidney Diseases 2015 65, 956-966DOI: (10.1053/j.ajkd.2015.01.026) Copyright © 2015 National Kidney Foundation, Inc. Terms and Conditions

Figure 5 (A) Low-power view of a transplant kidney biopsy specimen shows interstitial inflammation affecting >25% of the core in a acute cellular rejection (hematoxylin and eosin stain). (B) High-power view of the same specimen shows infiltration of the interstitium with round cells and macrophages, and “tubulitis” characterized by lymphocytic invasion of tubular basement membranes and entrance into the tubular lumen (arrows) (hematoxylin and eosin stain). American Journal of Kidney Diseases 2015 65, 956-966DOI: (10.1053/j.ajkd.2015.01.026) Copyright © 2015 National Kidney Foundation, Inc. Terms and Conditions

Figure 6 “Capillaritis” in a biopsy specimen from a patient with acute humoral rejection. Lymphocytes and granulocytes are present within peritubular capillaries (white arrows) (hematoxylin and eosin stain). American Journal of Kidney Diseases 2015 65, 956-966DOI: (10.1053/j.ajkd.2015.01.026) Copyright © 2015 National Kidney Foundation, Inc. Terms and Conditions

Figure 7 Trends in the use of immunosuppressant drug classes between 1998 and 2011 at the time of hospital discharge (dark lines) and at 1 year post-tx (light lines). Abbreviations: IL2-RA, interleukin 2 receptor antibody; mTOR, mammalian target of rapamycin; tx, transplantation. Reproduced from the 2011 Annual Data Report of the Organ Procurement and Transplantation Network (OPTN) and Scientific Registry of Transplant Recipients (SRTR). American Journal of Kidney Diseases 2015 65, 956-966DOI: (10.1053/j.ajkd.2015.01.026) Copyright © 2015 National Kidney Foundation, Inc. Terms and Conditions