Introduction Major histocompatibility complexes (MHC) are cell surface expressed proteins that bind to protein peptides in a surface groove present bound peptides to receptors on circulating T-cells participate in the activation of the adaptive immune response MHC are encoded by HLA genes that are localized to several different genetic regions different HLA regions encode for different types of MHC Allogenic MHC can be recognized by T-cells of the adaptive immune system mismatch of MHC is an important cause of transplant rejection MHC Classes There are two different classes of MHC encoded in the human genome class I MHC usually presents endogenous antigens to CD8+ killer T-cells class II MHC usually presents endocytosed antigens to CD4+ helper T-cells antigens may be "cross-presented" by the other MHC class in some cases The two MHC classes differ in several characteristics including HLA loci that encodes the gene sites of expression protein structure antigen loading site antigen loading mechanism binding partners Differences Between MHC Classes Feature MHC Class I MHC Class II HCA Loci HLA-A HLA-B HLA-C One letter HLA-DP HLA-DQ HLA-DR Two letters Site of expression All nucleated cells Platelets Antigen presenting cells Protein structure 1 long chain composing antigen binding site 1 short chain called β2 - microglobulin 2 equal length chains Additional invariant chain Antigen loading site Rough endoplasmic reticulum (RER) Acidified endosomes Loading mechanism Endogenous proteins are degraded by the proteosome Antigenic peptides are transported into the RER by the TAP transporter Antigens bind to MHC molecules directly Exogenous proteins are endocytosed from the cell surface Antigens are produced by degradation within the endosomal compartment Antigens bind to MHC molecules after release of the invariant chain Binding Partners T-cell receptor CD8 co-receptor T-cell receptor CD4 co-receptor Disease Associations Each individual possesses a set of MHC class I and class II subtypes these "haplotypes" define the peptides that will be recognized Some haplotypes are associated with specific diseases because they may preferentially bind to certain self-peptides lead to a failure of immune tolerance MHC Subtypes Associated With Diseases Class I Haplotype Diseases Class II Haplotype Diseases A3 Hemochromatosis DQ2/DQ8 Celiac disease B8 Addison disease Myasthenia gravis Graves disease DR2 Multiple sclerosis Hay fever Systemic lupus erythematosis Goodpasture syndrome B27 Psoriatic arthritis Ankylosing spondylitis Inflammatory bowel disease Reactive arthritis DR3 Diabetes melliutus type I Systemic lupus erythematosis Graves disease Hashimoto thyroiditis Addison disease DR4 Rheumatoid arthritis Diabetes mellitus type 1 Addison disease DR5 Pernicious anemia Hashimoto thyroiditis