Prof.

Ileana Constantinescu
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 Immunogenetics – a part of genetics which studies the
complexity of immune processes, concerning defense
and integrity of the host.

 MHC – encodes a group of highly diverse cell surface

proteins. There are two types of MHC molecules: class
I and class II molecules.

 Polymorphism – each MHC locus can express any one

of hundreds of different molecules.

 Its genes are codominantly expressed.

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 .

The structure of HLA class I molecules

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The structure of HLA class II molecules

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 HLA Genetics
•HLA alleles set found on one chromosome represents a haplotype.

•Each individual inherits two MHC haplotypes from each parent and
thus he has two alleles for each gene.

•These alleles are codominantly expressed.

•The inheritence of MHC genes follows the Mendel segregation rules.

Father Mother

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 2 digits

HLA-DRB1*13
A group of alleles which encode the DR13 antigen, i.e. there 62
DRB1*13 alleles: 1301 to 1362

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 4 digits

HLA-DRB1*1301

A specific allele

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 8 digits

HLA-DRB1*13010102

An allele which contains a mutation outside the coding region

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 4 digits

HLA-DRB1*1301N

A null allele N

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 8 digits

HLA-DRB1*13010102N

A null allele N which contains a mutation outside the

coding region

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 4 digits

HLA-DRB1*1301L

L indicated that the allele is low expressed at the cell surface

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 4 digits

HLA-DRB1*1301S

S indicated that the alleles is secreted but not stable at the

cell surface, find at soluble form

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 4 digits

HLA-DRB1*1301C

C indicated that the allele is present in the cytoplasm but not at the cell
surface

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 Host immune response against allograft
 Direct antigen presentation

 The response of recipient T cells to intact MHC/peptide

complexes on APCs from a graft is called direct
allorecognition.

 That is APCs in the graft directly present alloantigens (the

foreign MHC molecules) for recognition by alloreactive T cells.

 A recipient’s T cells can also react to donor MHC peptides

presented on the recipient’s own APCs. This pathway is called
indirect allorecognition.
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 Clinical signification
 Successful transplantation relies upon the immunologic compatibility
of recipients and their organ donor.

 This compatibility depends on both, the extent of matching of the

tissue types (HLA types) of donor and recipient and the absence of any
pre-existing antibody reactivity of the recipient with the donor.

 Both these factors influence the degree of immunosuppression

required to prevent rejection of the graft by the recipient.

 The key element to successful transplantation is the ability to correctly

identify the tissue types of recipients and donors and to predict
whether a graft is likely to be rejected ( host –versus graft disease) or in
the case of a BMT whether the graft will attack the recipient ( graft –
versus host disease GvHD)
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