Presented By; B. Om Preeti Singh (M.V.Sc. Microbiology)C.V.Sc. & A.H ,N.D.U.A&T. Faizabad, U.P.
MHC ◦ Cluster of genes found in all mammals ◦ MHC Act As Antigen Presenting receptors and are called as histocompatability molecules. involved in ◦ cell-cell interaction ◦ antigen presentation ◦ recognition of self-nonself molecules - Participant in both humoral and cell- mediated immunity
In Human, MHC Is Found On Chromosome 6 ◦ Referred to as HLA complex HLA genes are very diverse (polymorphic) i.e. there are many alleles of the class I and II genes In Mice, MHC Is Found On Chromosome 17 ◦ Referred to as H-2 complex In dogs – DLA complex In rabbits – RLA complex In chickens – B complex In bovines – BoLA and so forth
Class I MHC ◦ almost all nucleated cells ◦ antigen presentation to cytotoxic T cells ◦ Found In Regions A, B and C In Humans (K and D In Mice) Class II MHC ◦ on antigen-presenting cells ◦ antigen presentation to helper T cells ◦ Found In Regions DR, DP and DQ (IA and IE In Mice) These molecules are cell-surface glycoproteins class I and Class II MHC Share Structural Features ◦ Both involved in APC
Class III- MHC genes - secreted proteins( Products that include secreted proteins that have immune functions.) ◦ complement components ◦ Inflammation Class III MHC Have No Structural Similarity To Class I and II
Identified by cytotoxic T cells a chain noncovalently attached to b2-microglobulin association required for expression of class I molecules on the cell surface Peptide-binding cleft located on top of the surface of Class I – between a1 and a2 a chain is a transmembrane glycoprotein
a chain ◦ a1, a2, a3 – on outside of membrane ◦ transmembrane domain ◦ cytoplasmic tail b2-microglobulin ◦ similar to a3 ◦ no transmembrane region
Total no . Of class I loci varies In humans about 20 In mice 30, but all these are not functional In humans the functional loci are A,B,C, In mice K,D Others are pseudo genes that cannot be expressed.
* Between the class I and class II gene loci, there is a third locus (Class III)* This locus contains genes encoding tumor necrosis factor, lymphotoxin and two complement components (C2 and C4)* Class III antigens do not participate in MHC restriction or graft rejection
* Class I MHC antigens are : HLA-A, HLA-B and HLA-C* These antigens are glycoproteins found on surfaces of all nucleotide human cells and on platelets* HLA-A contains 24 different antigenic specificities, HLA-B contains 52 and HLA-C contains 11* Class I MHC antigens are involved of MHC restriction of cell mediated cytotoxicity
* Endogenously processed cytosolic peptides in virus infected cells or tumor cells are transported to the surface of the cells* They bind to MHC I molecules to be recognized by cytotoxic T-cells which then kill these cells* In other words; T-cells are only activated when they recognize both antigen and class I MHC molecules in association
Recognized by helper T cells HLA-DR Structure ◦ External domains, transmembrane segment and cytoplasmic anchor 4 exterior domains – a1, a2, b1, b2
Class II antigens are: HLA-DP, HLA-DQ, HLA-DR antigensThese antigens are glycoproteins found on the surface of macrophages, B-cells, Dentritic cells, langerhans cells of skin and activated T cellsHLA-DP contain 6 different antigenic specificities, HLA-DQ contains 9 and HLA-DR contains 20
Helper T-cells recognize antigens on antigen- presenting cells only when the antigens are presented on the surface of cells in association with class II MHC* Class II antigens react with the CD4 molecule on the helper T-cells which secrete cytokines
MHC Class I MHC Class IINomenclature HLA-A, HLA-B, HLA-C HLA-DP, HLA-DQ, HLA-DR Found on All nucleated somatic cells Macrophages, B-cells, Dentritic cells, langerhans cells of skin and activated T cellsRecognized by CD8 TC cells CD4 TH cells Functions Presentation of Ag to TC cells leading to Presentation of Ag to TH cells which secrete elimination of tumor or cytokines infected host cell
both class I and class II molecules can induce a response that leads to graft rejection MHC antigens also appear to play a role in development of auto diseases both class I and class II molecules play a major role in antigen presentation
They essentially determine the types of peptides to which an individual can mount an immune response. Although the MHC molecules typically have a broad binding capacity, small biochemical differences in these proteins are responsible for differences seen in the ability to react to a specific antigen. Thus individual’s MHC type for numerous reasons must be known.
For eg. hepatitis B Do not have the genetic capacity to respond. But, presence of a particular MHC protein may conferadditional protection. vaccines containing certain amino acid sequences that serve as immunodominant epitopes can be specifically developed. This might avoid the risk associated with using live organisms.
Additionally, if an individual suffers from allergies, knowing a person’s MHC type may predict the types of allergens It is likely that knowledge of the MHCmolecules will affect many areas of patient care in the future.