The document discusses the major histocompatibility complex (MHC) in mammals. It notes that MHC acts as antigen presenting receptors and are involved in cell-cell interaction, antigen presentation, and recognition of self and non-self molecules. MHC is found on chromosome 6 in humans and is referred to as the HLA complex. MHC molecules are divided into three main classes - Class I MHC present antigens to cytotoxic T cells, Class II MHC present antigens to helper T cells, and Class III MHC genes encode complement components and cytokines. The structures and functions of Class I and Class II MHC molecules are described in detail.
1. Presented By;
B. Om Preeti Singh
(M.V.Sc. Microbiology)
C.V.Sc. & A.H ,N.D.U.A&T.
Faizabad, U.P.
2.
3. 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
4. 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
5. 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
6.
7. 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
8.
9. 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
10.
11.
12. a chain
◦ a1, a2, a3 – on outside of membrane
◦ transmembrane domain
◦ cytoplasmic tail
b2-microglobulin
◦ similar to a3
◦ no transmembrane region
13. 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.
14.
15. * 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
16. * 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
17. * 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
18. Recognized by helper T cells
HLA-DR
Structure
◦ External domains, transmembrane segment and cytoplasmic
anchor
4 exterior domains – a1, a2, b1, b2
19.
20. Class II antigens are: HLA-DP, HLA-DQ, HLA-DR
antigens
These antigens are glycoproteins found on the
surface of macrophages, B-cells, Dentritic cells,
langerhans cells of skin and activated T cells
HLA-DP contain 6 different antigenic specificities,
HLA-DQ contains 9 and HLA-DR contains 20
21. 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
22. MHC Class I MHC Class II
Nomenclature 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 cells
Recognized 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
24. 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
25. 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.
26. 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.
27. 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.
