2017 EFI/DGI Meeting Teaching Session I

Transcription

1 2017 EFI/DGI Meeting Teaching Session I Mannheim, Wednesday, :30 12:00 Role of non-classical HLA in Stem Cell Transplantation 10:30 10:40 Non Classical HLA-Molecules J. Mytilineos, Ulm 10:40 11:05 HLA-E in stem cell transplantation C. Tsamadou, Ulm, DE 11:05 11:25 HLA-G in stem cell transplantation V. Rebmann, Essen, DE 11:25 11:45 MICA in stem cell transplantation I R. Carapito, Strassbourg, FR 11: MICA in stem cell transplantation II J. Mytilineos, Ulm, DE 11:55 12:00 General Discussion and Closure

2 2017 EFI/DGI Meeting Teaching Session I Mannheim, Wednesday, :30 12:00 Role of non-classical HLA in Stem Cell Transplantation Please don t forget to complete the evaluation questionaire (Survey) in your App after the session has been completed!

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4 Non-Classical HLA-Molecules Mannheim, Joannis Mytilineos MD, PhD Department of Transplantation Immunology Institute for Clinical Transfusion Medicine and Immunogenetics German Red Cross Blood Transfusion Service, and Department of Transfusion Medicine - University Clinic Ulm Ulm, Germany

5 Human MHC J. Mytilineos Mannheim 2017

6 Classical HLA-Class I (MHC 1a) HLA-A, -B, -C Non-Classical HLA-Class I (MHC 1b) HLA-E, -F, -G HLA-Class I Related Antigens MICA, MICB Classical HLA-Class II Antigens HLA-DR, -DQ, DP Non Classical HLA-Class II Structures HLA-DM, -DO MHC Antigens

7 Non Classical and MHC Related Polymorphism Structures Gene E F G MICA MICB DMA DMB DOA DOB Alleles Proteins Nulls

8 Non Classical MHC (Ib) Rachel L Allen, St George's, University of London, London, UK L Hogan, St George's, University of London, London, UK Are usually nonpolymorphic and tend to show a more restricted pattern of expression than their MHC Ia counterparts. May be recognised by specific subsets of T cell receptors or by innate immune receptors. Owing to their recognition by a more restricted set of receptors, MHC Ib are able to elicit a rapid response from immune cells and are, therefore, regarded as part of the innate immune system. Some MHC Ib act as antigen presenting structures, whereas others are recognised as direct ligands for immune receptors.

9 Non Classical MHC (Ib)

10 MHC Class I Related Structures

11 Non Classical and MHC related Structures Receptors HLA-E HLA-F HLA-G MICA and MICB CD94 NKG2A-C αβtcr LiLRB1 LiLRB2 Antigen in PG Short peptides Empty KIR2DS4 LiLRB1 LiLRB2 NKG2D γδtcr Short peptide Empty Heavy chain α1, α2, α3 α1, α2, α3 α1, α2, α3 α1, α2, α3 ß2 Assoc. Yes Yes Yes and No No Cell Attachm. Transmembr. Transmembr. Transmembr. Transmembr. Expression Ubiquitous Act. Lymph. Trophoblast Stress induced

12 Non Classical and MHC Ib - Functions

13 Non Classical HLA Class II Molecules Two other class II-like proteins are produced from the class II region of the MHC, HLA-DM (DM) and HLA-DO (DO) (called H2-M, or H2-DM and H2-O in the mouse). The function of DM is well established; it promotes peptide loading of class II molecules in the endosomal/lysosomal system by catalyzing the release of CLIP peptides (derived from the class II-associated invariant chain) in exchange for more stably binding peptides. While DM is present in all class II- expressing antigen presenting cells, DO is expressed mainly in B cells. In this cell type the majority of DM molecules are not present as free heterodimers but are instead associated with DO in tight heterotetrameric complexes. The association with DM is essential for the intracellular transport of DO, and the two molecules remain associated in the endosomal system. DO modulates HLA-DM function, with consequences for the spectrum of MHCbound epitopes presented at the cell surface for interaction with T cells Alfonso et al, Annu Rev Immunol. 2000;18: ; and Mellins et al Curr Opin Immunol Feb; 0:

14 HLA-DM and DO Function

15 Non Classical and MHC Related Structures Role in Antigen Procession, and Antigen Recognition Innate Immunity Pathways Tolerance Development Autoimmunity Cancer Response Infection Control? Transplantation?

16 2017 EFI/DGI Meeting Teaching Session I Mannheim, Wednesday, :30 12:00 Role of non-classical HLA in Stem Cell Transplantation 10:30 10:40 Non Classical HLA-Molecules J. Mytilineos, Ulm 10:40 11:05 HLA-E in stem cell transplantation C. Tsamadou, Ulm, DE 11:05 11:25 HLA-G in stem cell transplantation V. Rebmann, Essen, DE 11:25 11:45 MICA in stem cell transplantation I R. Carapito, Strassbourg, FR 11: MICA in stem cell transplantation II J. Mytilineos, Ulm, DE 11:55 12:00 General Discussion and Closure