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MHC (Genetic Variants (POLYGENISM (several genes for class I/II, different…
MHC
Genetic Variants
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Immune Evasion
bc huge role in initiating adaptive response, target for immune evasion
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2 strategies to present this - more than one type of MHC per person (fixed over lifetime) AND extensive population level differences in MHC catalouge
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Point Mutations
most are SNPs in binding site, non-synonymous - suggesting increased selection pressure for MHC polymorphisms
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Pathogens evade - 60% china/png have HLA-A11 for EBV presentation, many EBV isolates in this area evolved to evade
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RA
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new data revealed most significant association was with 2 aa at position 11 (peptide binding groove) of HLA-DR heterodimer
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Introduction
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suite of genes on Chr 6 short arm encoding cell surface proteins important in initiating T cell response
new dense genotyping platforms helping to overcome difficulty of identifying MHC alleles due to high LD and variation
MHC + autoimmune disease first described in 1970s - remain strongest risk factors for autoimmune diseases
Physiological Role
recognise, bind and present antigen fragments from infected cells
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T cells not stimulated by soluble native Ag/cell surface peptides, on through MHC presentation
Class I
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Structure 
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B2m non-covalently bound to alpha 1 domain, non-MHC encoded
alpha 3 and beta 2m homologous to IgC (immunoglobulin superfamily) - structurally and in AA composition
peptide binding cleft between alpha 1 and 2 domain - consists of two segments peptide alpha helices and floor of 2 anti-parallel beta strands
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Polymorphisms
1300 alleles, B had most when studied in 2005 (699)
Class II
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Structure
34kDa alpha chain, 29kDa beta chain - both anchored
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Polymorphisms
700 alleles - high in DRB1 and DPB1
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HIV
HLA-B*35-PY slower progression to AIDS - increased CD8+ T cell response to HIV peptide fragements like Gap p24
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