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3-11 - Each individual expresses multiple forms of MHC in...

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Each individual expresses multiple forms of MHC in order to present diverse antigens. Paternal allele Class I MHC A B C α β β β α α DP DQ DR Class II MHC Human MHC: HLA (Human Leukocyte Antigen) Maternal allele A B C α β β β α α β 2 microglobulin ( β 2M) 6 class I MHC 4 DR 4 DQ 4 DP α β 12 or more class II MHC Some people have more than one DR β gene. β 2M A, B, C Mouse MHC: H-2 Class II MHC: H2-IA, H2-IE; Class I MHC: H2-K, H2-D
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There are many forms of MHC genes (polymorphic) within a population. Different HLA alleles have Different affinities for peptides. Induce different T cell responses. Designation HLA-A1, HLA-A3 … HLA-DR1, HLA-DR15 … The variable residues are concentrated in antigen binding groove. Haplotype A1 B8 Cw4 DR15 DQ2 DPw6 A3 B7 Cw1 DR7 DQ5 DPw3
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Antigen Presentation Antigen presenting cells (APC) Dendritic cells, B cells, Macrophages APCs express both MHC and co-stimulatory molecules. Only APCs can activate naïve T cells. T cell APC MHC/antigen TCR/CD8 and CD4 Class I and II B7 CD28 Co-stimulation Antigenic stimulation Non-APC T cell TCR/CD8 CD28 MHC-I/antigen activation No co-stimulation No activation
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Presentation of endogenous antigen by class I MHC Endogenous cytosolic protein ubiquitination peptides proteasome ER TAP chaperon proteins Gogi MHC-I leaves ER after loading with peptides. Empty MHC-I is held by chaperons in ER. TAP deficiency prevents surface expression of MHC-I.
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Immunoproteasome β 1, β 2, and β 5 subunits contain protease active sites. β 1i (LMP2), β 2i (MECL-1), β 5i (LMP7) replace β 1, β 2, and β 5 in immunoproteasomes. These proteases are constitutively expressed in APCs. They are induced by γ -interferon in non-APCs. Immunoproteasomes produce peptides that have hydrophobic residues at the C-terminus. P9 anchor residues for class I MHC are mostly hydrophobic. γ -interferon also induces the expression of proteasome activator 28 (PA28). PA28 stimulates proteasome activity. Many genes involved in antigen presentation are within MHC loci. *
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Presentation of exogenous antigen by class II MHC phagocytosis macrophinocytosis endocytosis endosomes ER Class II MHC Gogi Invariant chain Invariant chain prevents binding of Endogenous peptides to MHC-II.
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