Prof. Ileana ConstantinescuProf. 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 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 alleles set found on one chromosome represents a haplotype.

HLA Genetics

•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*1301HLA-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*1301NHLA-DRB1*1301N

A null allele N

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8 digits

HLA-DRB1*13010102NHLA-DRB1*13010102N

A null allele N which contains a mutation outside the coding region

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4 digits

HLA-DRB1*1301LHLA-DRB1*1301L

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

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4 digits

HLA-DRB1*1301SHLA-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*1301CHLA-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.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 compatibilityof recipients and their organ donor.

� This compatibility depends on both, the extent of matching of thetissue types (HLA types) of donor and recipient and the absence of anypre-existing antibody reactivity of the recipient with the donor.

� Both these factors influence the degree of immunosuppressionrequired to prevent rejection of the graft by the recipient.

� The key element to successful transplantation is the ability to correctlyidentify the tissue types of recipients and donors and to predictwhether a graft is likely to be rejected ( host –versus graft disease) or inthe case of a BMT whether the graft will attack the recipient ( graft –versus host disease GvHD)

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