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MHC _ Major Histocompatibility Complex_

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MHC _ Major Histocompatibility Complex_ Powered By Docstoc
					              MHC
( Major Histocompatibility Complex)

I. Concepts
II. Organization of MHC
III. genetic characteristics of MHC
IV . MHC molecules
V. Interaction of antigenic peptides with MHC
molecules
VI. Biologic activities of MHC
Part I. Some concepts
1.Histocompatibility Ag
Antigens which cause immune response
to the graft and determine the survival of
the graft.
2.MHS(Major histocompatibility antigen
system )
A group of complex histocompatibility
antigens which cause rapid and strong
immunoreaction to the graft .
3.MHC (Major histocompatibility
complex)
A cluster of genes which encode for
major histocompatibility antigens
and relate to immune response.
4.HLA (human leucocyte antigen)
The major histocompatibility antigens of
human which are associated with
histocompatibility and immune response.
5.HLA complex
The MHC of human, a cluster of the
genes which encode for HLA and relate
to histocompatibility and immune
response.
6.H-2 complex
 The MHC of mice
Part II.Organization of HLA complex
 Located on chromosome 6.
● Class I gene region
    1. classical HLA I genes-------HLA-A,B,C gene loci
    2. non-classical HLA I genes----HLA-E,F,G
    3. MHC I chain-related genes
●   Class II gene region
     1. classical HLA II genes---HLA-DP,DQ,DR
subregion
   (2 or more than 2 gene loci in each subregion)
  2. genes associated with antigen processing
●   Class III gene region
      complement genes-----C4,C2,B
     inflammation-associated genes----TNF,HSP70
 Located on chromosome 6.
● Class I gene region
  1. classical HLA I genes-------HLA-A,B,C
gene loci
  2. non-classical HLA I genes----HLA-
E,F,G
  3. MHC I chain-related genes
●   Class II gene region
     1. classical HLA II genes---HLA-
DP,DQ,DR subregion
    (2 or more than 2 gene loci in each
subregion)
   2. genes associated with antigen
processing
HLA-DM gene

TAP gene (transporter associated with
antigen processing)

PSMB gene (Proteasome subunit, beta
type )

HLA-DOA and HLA-DOB genes
●   Class III gene region
   complement genes-----C4,C2,B
  inflammation-associated genes----
TNF,HSP70
III. Genetic characteristics of MHC

1. Polymorphism:
 Multiple alleles
 In a population, there are multiple alleles at a gene
locus of MHC
 Codominance
The two alleles at a gene locus of MHC in the two
homogenous chromosomes are expressed together.
.
2. Haplotype
 A gene combination which results
from gene loci linked in a chromosome.
3. Linkage disequilibrium
The probability in which two or more
than two alleles present together in
one chromosome is greater than the
probability in which they present
randomly,that is ,the distribution of
haplotypes is not random in a
population
Diversity -----MHC molecules are
diverse.

 Diversity is generated by natural
selection and show life-force.
Part IV. MHC molecules

I) Molecular structure

II) Distribution
I. Molecular Structure of HLA
1. HLA class I molecules
1) two separate polypeptide
  chains
n MHC-encoded alpha (or
  heavy) chain;
n non-MHC-encoded      beta
  chain (beta2 microglobulin)
2) Only alpha chain spans
  the membrane
3)The molecule has four domains
a1 domain, a 2 domain
  interact to form a peptide-binding
  region ( A peptide 8-10 amino
  acids long sits in the groove.)

 a3 domain ,
 combining site of CD8
  b 2 microglobulin domain
refered to as immunoglobulin-like
   region to maintain their proper
   conformation.
2.Class II HLA
1) two chains, a and b. both
  are MHC-encoded
2)both a and b chain span
  the membrane.
3) four domains
a 1 and b 1
     form the peptide-binding
  region
a 2 and b 2
  form the immunoglobulin-like
  region. b 2 : Combining site of
  CD4
II) Distribution of HLA molecules
1.class I molecules
In human, all nucleate cells carry the
  class I antigens in variant amounts
2.class II molecules
  Activated Tcells,
  Professional antigen-presenting
  cells (macrophages, dentritic cells
  and B cells),
  Thymus epithelial cells et al.
    Part V. Interaction of HLA molecules
    and antigen peptides
n   Combination of antigen peptide and
    antigen-binding groove
n   Molecular basis of the interaction of
    HLA molecules and antigen peptides
n   Characteristics of MHC molecules-
    antigen peptides interaction
1. Combination of antigen peptide
   and antigen binding groove
                                 a1
MHC-I 分子


       COOH                                         a 螺旋
     (衔 接 a3)
                                                  肽槽


                NH2                               a 螺旋
                                           a2


                      a1                    NH2

                                                  COOH(衔 接 a2)

MHC-II 分子                                                a 螺旋

                                                     肽槽
        COOH
                                                       a 螺旋
    (衔 接 b2)




                                      b1
                           NH2
n Class I MHC molecule
A peptide 8-10 amino acids long sits in the
  groove.
 The greatest variability in amino acids occurs in
  the a1 and a 2 sequences
n Class II MHC molecule
A peptide 13-17 amino acids long sits in the
  groove.
2.Molecular basis of the interaction of HLA
  molecules and antigen peptides
Anchor sites
 binding sites of an antigen peptide bound with
  antigen-binding grooves of MHC molecules
anchor residues
 amino acids in the
 anchor sites bind
to antigen- binding
grooves of
 MHC molecules.
NH2    抗原肽                    C00H




      凹槽           锚定位(锚定残基
                   )
             MHC-II分子
             MHC-II分子
Anchor sites : places of the anchor residues
3. Characteristics of MHC
molecules/anigen peptides interaction
 relative specificity
(1) Specificity
     Certain MHC molecule
     recognizes corresponding
     consensus motif
 (2) Flexibility
     Amino acids “x” and anchor
     residue are variable
    Different MHC molecules can
     recognize similar consensus
Part VI. Biologic activities of HLA
1. induce the differentiation of T cell to
  form T cell repertoire

2. present antigens to initiate immune
  response
n   Endogenous Ag is presented to CD8 T cell by
    MHC class I molecule
n   Exogenous Ag is presented to CD4 T cell by
    MHC class II molecule
Application of HLA in medicine
1.HLA in transplantation
2.some diseases are associated with HLA
  genotypes

				
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posted:7/25/2013
language:English
pages:50