Major Histocompatibility ComplexChapter 7.ppt

Major Histocompatibility ComplexChapter 7 MHC Major Histocompatibility Complex Cluster of genes found in all mammals Its products play role in discriminating self/non-self Participant in both humoral and cell-mediated immunity MHC Act As Antigen Presenting Structures In Human MHC Is Found On Chromosome 6 Referred to as HLA complex In Mice MHC Is Found On Chromosome 17 Referred to as H-2 complex MHC Genes Of MHC Organized In 3 Classes Class I MHC genes Glycoproteins expressed on all nucleated cells Major function to present processed Ags to TC Class II MHC genes Glycoproteins expressed on M?, B-cells, DCs Major function to present processed Ags to TH Class III MHC genes Products that include secreted proteins that have immune functions. Ex. Complement system, inflammatory molecules Class I, II and III MHC Class I MHC Genes Found In Regions A, B and C In Humans K and D In Mice Class II MHC Genes Found In Regions DR, DP and DQ IA and IE In Mice Class I and Class II MHC Share Structural Features Both involved in APC Class III MHC Have No Structural Similarity To Class I and II Ex. TNF, heat shock proteins, complement components MHC Genes Are Polymorphic MHC Products Are Highly Polymorphic Vary considerably from person to person However, Crossover Rate Is Low 0.5% crossover rate Inherited as 2 sets one from father, one from mother Haplotype refers to set from mother or father MHC Alleles Are Co-dominantly Expressed Both mother and father alleles are expressed Inbred Mice Haplotypes Are Designated With Italic Superscript Ex. H-2b Designation refers to entire set of H-2 alleles Inheritance Of HLA Haplotypes Class I MHC Molecule Comprised of 2 molecules ? chain 45 kDa , transmembrane ?2-microglobulin 12 kDa Non-covalently associated with each oth Association Of ? Chain and ?2 Is Required For Surface Expression ? Chain Made Up Of 3 Domains ?1, ?2 and ?3 ?2-microglobulin Similar To ?3 ?1 And ?2 Form Peptide Binding Cleft Fits peptide of about 8-10 a/a l