HLA Typing-Immunology

HLA TYPING
What is HLA typing ?

 HLA stands for Human Leukocyte Antigen, but it is always referred to as
HLA. HLA typing is also sometimes called HLA matching. It is a diagnostic
test.
 HLA typing is a kind of genetic test used to identify certain individual
variations in a person’s immune system. The process is critical for identifying
which people can safely donate bone marrow, cord blood, or an organ to a
person who needs a transplant.
 They are the antigens found in the surface of human leukocytes i.e. the Major
Histocompatibility Complex (MHC).
 These MHC complex are the genes that is located on the short arm of
Chromosome 6.
CLASSIFICATION
Interacts with Interacts with
CD8+ CD4+
T-Lymphocytes T-Lymphocytes
CLASS III
HLA-A HLA-DP
CLASS II
Cytokines
CLASS I
HLA-B HLA-DQ DR2 Complement

System
HLA-C HLA-DR DR3
DR4
MHC I
 Class I molecules are made
up of one Heavy chain and a
Light chain
 Class I molecules are found in
all nucleated cells in the body
 MHC-I interacts with
peptides from Cytosolic
Degradation.
MHC II
 Class II molecules have two
Alpha and two Beta chains.
 These are present only in Antigen
presenting cells.
 MHC-II interacts with peptides
from Endocytic degradation.
Why should we learn about HLA typing ?
 Since differences in blood group and major histocompatibility antigens are
responsible for the most intense graft-rejection reactions, various tissue-typing
procedures to identify these antigens have been developed to screen potential
donor and recipient cells.
 Initially, donor and recipient are screened for ABO blood-group compatibility.
The blood-group antigens are expressed on RBCs, epithelial cells, and
endothelial cells. Antibodies produced in the recipient to any of these antigens
that are present on transplanted tissue will induce antibody-mediated
complement lysis of the incompatible donor cells.
The process of Graft rejection can be divided into two stages:
1. Sensitization phase – in which antigen-reactive lymphocytes of the recipient
proliferate in response to allo-antigens on the graft. During the sensitization
phase, CD4+ and CD8+ T cells recognize alloantigens expressed on cells of the
foreign graft and proliferate in response. Both major and minor histocompatibility
alloantigens can be recognized. In general, the response to minor
histocompatibility antigens is weak, although the combined response to several
minor differences can sometimes be quite vigorous. The response to major
histocompatibility antigens involves recognition of both the donor MHC molecule
and an associated peptide ligand in the cleft of the MHC molecule.
2. An Effector Stage – in which immune destruction of the graft takes place.
We will see two methods that are involved in HLA
typing…
 Microcytotoxicity Test
 Mixed-Lymphocyte Reaction (MLR)
MICROCYTOTOXICITY TEST
 In this test, white blood cells from the potential donors and
recipient are distributed into a series of wells on a
microtiter plate, and then antibodies specific for various
class I and class II MHC alleles are added to different
wells. After incubation, complement is added to the wells,
and cytotoxicity is assessed by the uptake or exclusion of
various dyes (e.g., trypan blue or eosin Y) by the cells.
 If the white blood cells express the MHC allele for which a
particular monoclonal antibody is specific, then the cells
will be lysed upon addition of complement, and these dead
cells will take up a dye such as trypan blue. HLA typing
based on antibody-mediated microcytotoxicity can thus
indicate the presence or absence of various MHC alleles.
Here, donor 1 shares HLA-A antigens recognized by antisera in wells 1 and 7
with the recipient, whereas donor 2 has none of HLA-A antigens in common
with the recipient.
MIXED-LYMPHOCYTE REACTION (MLR)
 Even when a fully HLA-compatible donor is not available, transplantation
may be successful. In this situation, a one-way mixed-lymphocyte reaction
(MLR) can be used to quantify the degree of class II MHC compatibility
between potential donors and a recipient.
 Lymphocytes from a potential donor that have been x-irradiated or treated
with mitomycin C serve as the stimulator cells, and lymphocytes from the
recipient serve as responder cells. Proliferation of the recipient T cells, which
indicates T-cell activation, is measured by the uptake of [3H]thymidine into
cell DNA. The greater the class II MHC differences between the donor and
recipient cells, the more [3H]thymidine uptake will be observed in an MLR
assay. Intense proliferation of the recipient lymphocytes indicates a poor
prognosis for graft survival.
MIXED-LYMPHOCYTE REACTION (MLR)
IMPORTANCE OF HLA TYPING
 The survival of kidney grafts depends primarily on donor-recipient matching of the HLA
class II antigens.
 Matching or mismatching of the class I antigens has a lesser effect on graft survival
unless there also is mismatching of the class II antigens. A two-year survival rate of 90%
is seen for kidney transplants in which one or two class I HLA loci are mismatched,
while transplanted kidneys with differences in the class II MHC have only a 70% chance
of lasting for this period.
 Those with greater numbers of mismatches have a very low survival rate at one year
after transplant.
 HLA matching is most important for kidney and bone-marrow transplants; liver and
heart transplants may survive with greater rate when compared with other organs.
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HLA TYPING

What is HLA typing ?

HLA-B HLA-DQ DR2 Complement

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