MHC Flashcards
is a genetic region, whose
products play a role in intracellular recognition and in discrimination between
self and non self.
major histocompatibility complex (MHC)
participates in the development of immune responses, especially T-
cell mediated immune response.
MHC
Mhc gene products
MHC gene products were identified as
responsible for graft rejection.
• In studies on responses to antigen, MHC gene products were found
to control immune response (Ir) genes.
recognize portions
of protein antigens that are bound non-covalently to MHC gene
products.
antigen-specific T cells
recognize peptide bound to class II MHC gene
products.
Helper T cells
recognize peptide bound to class I MHC gene
products.
Cytolytic T cells
• The complete three-dimensional structure for both class I and class
II MHC molecules has been determined by
X-ray crystallography
Class I MHC structure
•Class I MHC molecules are comprised of two polypeptides: a
polymorphic heavy chain and a non-polymorphic light chain called
B2 macroglobulin.
• The heavy chain is encoded within the MHC locus on chromosome
6, while the light non-polymorphic chain is encoded on chromosome
15.
• Each of the three forms of class I molecules, HLA-A, HLA-B, HLA-C
are composed on virtually all nucleated cells, although the number
of each HLA molecules (A,B and C) expressed on any given cell
MHC CLASS II structure
CLASS II MHC
• These molecules are comprised of two polypeptide chains
designated alpha and beta.
• Each of these chains is polymorphic and the genes that encode
then are located within the MHC locus.
• For the most part, class II MHC molecules HLA-DP, HLA-DQ, HLA-DR
are normally expressed on antigen presenting cells.
Peptide fragment of protein and vesicular proteins
TC and TH
Max number of gene products
• In general, peptide fragments of proteins in the cytosol associate
with class I MHC, those of vesicular proteins associate with class II
MHC.
• Each is recognize by functionally distinct T cell populations. Tc
recognize class I MHC and Th recognize class II MHC peptides.
• The maximum number of class I MHC gene products expressed in
an individual is six. That for class II MHC product can exceed six
but is also limited.
Mature T cells respond to foreign antigens, but not
self-protein
increase the level of
expression of class I and class II molecules.
Cytokines, especially interferon gamma (IFN gamma)
Although an individual may
not possess MHC molecules capable of binding certain antigenic peptides, say
for example against a virulent organism, the likelihood is great that other
MHC in the species can do so. Overall this affords an evolutionary protection
for the continuation of that species.
Why the high polymorphism of MHC molecules?
HLA-B27
ankylosing spondylitis
HLA-
DR4 allele.
rheumatoid arthritis
IMPORTANCE OF MHC
• Plays central role in the success or failure of organ
transplants
• Regulation of immune response
• Association with particular disease
MHC genetic regions
MHC GENETIC REGIONS
• Class I region: HLA-A, HLA-B, and HLA-C
• Class II region: HLA-DP, HLA-DR and HLA-DC
• Class II region: complement proteins
total set of MHC alleles inherited from one parent
Haplotype
– sum of haplotype
Genotype
How many clas of class 1 and 2 proteins and how many many copy of chrmosome 6
Each person inherits 2 copies of chromosome 6 and thus can
expressed up to 6 different class I and 6 different class II protein
– genes that determines the outcome of
the graft.
Histocompatibility genes
– protein encoded by those genes
Histocompatibility antigens
– 2 region – single locus responsible for graft
rejection.
Histocompatibility
