MMI188 Lec 10

MMI188 Lec 10 - Chapter 5! Antigen Recognition by T...

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Unformatted text preview: Chapter 5! Antigen Recognition by T Lymphocytes! MHC! MMI 188 2010! Human Immune System! Lecture 5! Chris Bowlus! clbowlus@ucdavis.edu ! T cell/MHC Interactions! MHC Class I Peptide Loading! MHC Class I Antigen Processing! Cytoplasmic, intracellular pathogens! 1.  2.  3.  4.  Degraded by proteasome! Peptide transported to ER! Binding to MHC class I in ER! Transport to cell surface! MHC Class I Caveats! Most peptides do not bind to MHC! Non-infected cells display self antigen! Do not illicit an immune response “tolerance”! Break in tolerance results in autoimmunity! MHC Class II Antigen Processing! Extracellular pathogens! 1.  2.  3.  4.  Endocytosis! Degradation in phagosome! Binding to MHC class II ! Transport to cell surface! MHC Class II Presentation! MHC Class II Chaperones! Invariant Chain! Directs MHC to endocytic vesicles! MHC class II compartment (MIIC)! CLIP! Product of Invariant Chain cleavage! Blocks binding of peptide! Removal is aided by interaction of MHC with HLADM! HLA-DM! MHC class II molecule! Does not bind peptide or appear on cell surface! Edited by Foxit Reader Copyright(C) by Foxit Corporation,2005-2009 For Evaluation Only. Differential Expression of MHC Molecules! Figure 3-22! *Activated T cells! antigen presenting cell Major Histocompatibility Complex! Major versus minor! Histo (tissue) compatibility for transplantation! Complex of genes! Edited by Foxit Reader Copyright(C) by Foxit Corporation,2005-2009 For Evaluation Only. Major Histocompatibility Complex! Skin graft to syngeneic recipient! MHCa! Skin graft to allogeneic recipient! MHCa! Skin graft to different Minor Histocompatibility recipient! MHCa! MHCa! MHCb! MHCa! not rejected Edited by Foxit Reader Copyright(C) by Foxit Corporation,2005-2009 For Evaluation Only. Achieving MHC Binding Diversity! •  No MHC gene rearrangement! •  Polygeneic! –  Multiple genes encode MHC class I and II proteins! •  Polymorphic! –  Multiple alleles of each gene are found in any population! •  Most individuals are heterozygous! Edited by Foxit Reader Copyright(C) by Foxit Corporation,2005-2009 For Evaluation Only. HLA Human Leukocyte Antigens = MHC! •  > 4 million bp on Chromosome 6! •  3 class I α chain genes (A, B, C)! –  β2-microglobulin is encoded on chromosome 15 and is not polymorphic or polygenic! •  3 class II molecules (DP, DQ, DR)! –  α and β chains encoded together! –  2 β chains encoded for DR! •  DRB1 and either DRB3, DRB4, DRB5 or none! Non-MHC Genes in the ! Class II Region! Edited by Foxit Reader Copyright(C) by Foxit Corporation,2005-2009 For Evaluation Only. MHC Genes are inherited as a haplotype! •  Haplotype! –  Specific combination of alleles on a part of a chromosome! –  Not randomly inherited (non-Mendelian)! •  Occasional recombination during meiosis! •  Human Leukocyte Antigens (HLA)! –  Minimally 3 class I and 3 class II isoforms! –  Up to 6 class I and 8 class II isoforms! 안중요하대 ㄷㄷㄷ Edited by Foxit Reader Copyright(C) by Foxit Corporation,2005-2009 For Evaluation Only. Figure 3-23! few alleles Edited by Foxit Reader Copyright(C) by Foxit Corporation,2005-2009 For Evaluation Only. Polymorphisms Cluster in Binding Groove! allows diff proteins to bind to different MHC Selection of MHC ! Evolution of New MHC Alleles! Heterozygous Advantage! CHAPTER 7! The Development of T Lymphocytes! Edited by Foxit Reader Copyright(C) by Foxit Corporation,2005-2009 For Evaluation Only. purple-developing T cells Edited by Foxit Reader Copyright(C) by Foxit Corporation,2005-2009 For Evaluation Only. initiate rearrangement Edited by Foxit Reader Copyright(C) by Foxit Corporation,2005-2009 For Evaluation Only. Edited by Foxit Reader Copyright(C) by Foxit Corporation,2005-2009 For Evaluation Only. cell cannot be gamma delta locus anymore Edited by Foxit Reader Copyright(C) by Foxit Corporation,2005-2009 For Evaluation Only. ...
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This note was uploaded on 02/16/2011 for the course MIC 105 taught by Professor Wheelis during the Spring '08 term at UC Davis.

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