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

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Unformatted text preview: Each individual expresses multiple forms of MHC in order to present diverse antigens. Paternal allele Class I MHC A B C DP DQ DR Class II MHC Human MHC: HLA (Human Leukocyte Antigen) Maternal allele A B C 2 microglobulin ( 2M) 6 class I MHC 4 DR 4 DQ 4 DP 12 or more class II MHC Some people have more than one DR gene. 2M A, B, C Mouse MHC: H-2 Class II MHC: H2-IA, H2-IE; Class I MHC: H2-K, H2-D There are many forms of MHC genes (polymorphic) within a population. Different HLA alleles have Different afFnities 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 Antigen Presentation Antigen presenting cells (APC) Dendritic cells, B cells, Macrophages APCs express both MHC and co-stimulatory molecules. Only APCs can activate nave 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 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 deFciency prevents surface expression of MHC-I. Immunoproteasome 1, 2, and 5 subunits contain protease active sites. 1i (LMP2), 2i (MECL-1), 5i (LMP7) replace 1, 2, and 5 in immunoproteasomes. These proteases are constitutively expressed in APCs. They are induced by -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. -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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3-11 - Each individual expresses multiple forms of MHC in...

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