2. HLA human leukocyte antigens: Alloantigen – differ among members of same species present on surface of cells, encoded on HLA genes Genes clustered on MHC, located on short arm of chromosome6. HLA Genes HLA-A, HLA-B, HLA-C → Class I MHC proteins HLA-D → DP, DQ, DR → Class II MHC proteins Class III Genes for → C2, C4, TNF, Lymphotoxin LT 2 haplotypes, maternal and paternal sets Polymorphic (many alleles) HLA-A – 47, HLA-B – 88, HLA-C – 29, HLA-D - 300 3. Every person has single allele at each locus. So inherit two haplotypes – 1 maternal on chromosome 6, 1 paternal set. Each allele can make 2 class I & 2 class II proteins. Co- dominant. Proteins by both are expressed. Each person can make 12 HLA proteins 3 each at class I and II loci, from both chromosomes Minor antigens by genes at other sites. Body proteins with 1 or more different amino acid → weak immune response → slow rejection of graft. 4. Class I MHC: glycoprotein. Present on All nucleated cells 20 proteins encoded by A, 40 by B, 8 by C gene locus 45,000 Mol. wt. Heavy chain non covalently bound to β2 microglobulin. Similar to Ig molecule. Highly polymorphic. Importance is recognition of self & non self. Hypervariable region at N terminal region. constant region binds to CD 8 of cytotoxic T cell 5. Class II MHC: glycoprotein. Highly polymorphic Present on Macrophages, B cell, Dendritic cell Spleen, Langerhans cell (skin) Made up of 2 polypeptides (mol wt. 33000, 28000) non covalently bound. Constant region for CD4 protein of helper T cell Functions of Major Histocompatibility Complex MHC 1. Positive selection of T cells in thymus 2. Antigen presentation 6. Present antigens to T cells which recognize antigen only if associated to self class I or II MHC → immune response - MHC restriction. Success of organ or tissue transplant - compatibility of donor & recipient MHC genes. If HLA proteins differ → immune response → rejection of graft. Minor antigens → slow rejection. Autoimmune diseases: occur in individuals who carry certain MHC genes 7. Auto graft: Transfer of individuals own tissue to another site in the body. Permanently accepted Syngeneic graft: Transfer of tissues between genetically identical individuals e.g identical twins Xenograft: Transfer between different species. Allograft: Transfer between members of same species. Usually rejected unless immunosuppressive drugs given e.g from one human to another. 8. Allografts are rejected by a process known as allograft reaction. In an acute allograft reaction; vascularization of the graft is normal initially, but in 11-14 days, marked reduction in circulation and mononuclear cell infiltration occurs, with eventual necrosis. This is called a primary (first-set) reaction A T-cell-mediated reaction is the main cause of rejection of many types of grafts, e.g., skin, but antibodies contribute to the rejection of certain transplants, especially bone marrow 9. If a second allograft from the same donor is applied to a sensi

1. MHC &
TRANSPLANTATION
PRESENTED BY: ARSLAN AMANAT

2. MAJOR HISTOCOMPATIBILITY
COMPLEX MHC
HLA human leukocyte antigens:
• Alloantigen – differ among members of same species
• present on surface of cells, encoded on HLA genes
• Genes clustered on MHC, located on short arm of chromosome6.
HLA Genes
• HLA-A, HLA-B, HLA-C → Class I MHC proteins
• HLA-D → DP,DQ, DR → Class II MHC proteins
• Class III Genes for → C2, C4, TNF, Lymphotoxin LT
• 2 haplotypes, maternal and paternal sets
• Polymorphic (many alleles) HLA-A – 47, HLA-B – 88, HLA-C – 29,
HLA-D - 300

3. MAJOR HISTOCOMPATIBILITY COMPLEX
MHC
HLA GENES
• Every person has single allele at each locus. So inherit
• two haplotypes – 1 maternal on chromosome 6, 1 paternal set.
• Each allele can make 2 class I & 2 class II proteins. Co- dominant.
Proteins by both are expressed.
• Each person can make 12 HLA proteins 3 each at class I and II loci,
from both chromosomes
Minor antigens by genes at other sites. Body proteins with 1 or more
different amino acid → weak immune response → slow rejection
of graft.

4. MHC PROTEINS
• Class I MHC: glycoprotein. Present on All nucleated cells
• 20 proteins encoded by A, 40 by B, 8 by C gene locus
• 45,000 Mol. wt. Heavy chain non covalently bound to β2
microglobulin. Similar to Ig molecule. Highly polymorphic.
Importance is recognition of self & non self. Hypervariable region
at N terminal region. constant region binds to CD 8 of cytotoxic T
cell

5. MHC PROTEINS
• Class II MHC: glycoprotein. Highly polymorphic
• Present on Macrophages, B cell, Dendritic cell Spleen, Langerhans cell
(skin)
• Made up of 2 polypeptides (mol wt. 33000, 28000) non covalently bound.
Constant region for CD4 protein of helper T cell
Functions of Major Histocompatibility Complex MHC
• 1. Positive selection of T cells in thymus
• 2. Antigen presentation

6. BIOLOGIC IMPORTANCE OF MHC
PROTEINS
• Present antigens to T cells which recognize antigen only if
associated to self class I or II MHC → immune response - MHC
restriction.
• Success of organ or tissue transplant - compatibility of donor &
recipient MHC genes. If HLA proteins differ → immune response
→ rejection of graft. Minor antigens → slow rejection.
• Autoimmune diseases: occur in individuals who carry
• certain MHC genes

7. TRANSPLANTATION
• Auto graft: Transfer of individuals own tissue to another site in
the body. Permanently accepted
• Syngeneic graft: Transfer of tissues between genetically identical
individuals e.g identical twins
• Xenograft: Transfer between different species.
• Allograft: Transfer between members of same species. Usually
rejected unless immunosuppressive drugs given e.g from one
human to another.

8. ALLOGRAFT REJECTION
• Allografts are rejected by a process known as allograft reaction.
In an acute allograft reaction;
• vascularization of the graft is normal initially, but in 11-14 days,
marked reduction in circulation and mononuclear cell infiltration
occurs, with eventual necrosis.
• This is called a primary (first-set) reaction
• A T-cell-mediated reaction is the main cause of rejection of many
types of grafts, e.g., skin, but antibodies contribute to the rejection of
certain transplants, especially bone marrow

9. ALLOGRAFT REJECTION
• If a second allograft from the same donor is applied to a sensitized recipient,
it is rejected in 5-6 days
• This accelerated (second-set) reaction is caused primarily by presensitized
cytotoxic T cells
• Class I & II MHC determine rejection or acceptance. class II – major role
esp. DR
• Foreign MHC activate more T cells
• CD8-positive cytotoxic T cells do most of the killing of the
• allograft cells

10. ALLOGRAFT REJECTION
Stimulation of recipients immune system by 3 processes:
1. Donors APC present self (donor) proteins in association with donor
MHC.
2. Donors APC present recipient proteins with donor MHC.
3. Recipient s APC present donor protein with recipient MHC.

11. ALLOGRAFT REJECTION
Chronic rejection:
• Graft become non functional months to years later. Cause: Atherosclerosis,
incompatibility of minor HLA protein, side effects of immunosuppressive drugs
Hyper acute rejection or white graft reaction:
• Rejection within minutes of engraftment due to preformed antiABO antibodies in
recipient with ABO antigens on endothelium of graft. Spasm / occlusion of blood
vessels → loss of blood supply → Graft white. ABO cross matching important.
Fetus allograft:
• Paternal MHC genes foreign to mother, yet no rejection. Reason unclear.
Trophoblastic layer may not allow maternal T cells to enter fetus.

12. HLA TYPING IN LAB
To determine the closest MHC match between donor and recipient
• DNA sequencing using PCR to determine different class I & II
alleles by specific probes on both chromosomes. Method of choice,
Specific & sensitive
• Serologic assays: cells from donor and recipient are reacted with a
battery of antibodies, for specific class I & class II proteins. Addition
of complement→ lysis of cell. Less sensitive. Cannot detect certain
alleles.

13. HLA TYPING IN LAB
Mixed lymphocyte culture MLC or MLR reaction
• Stimulator lymphocytes from potential donor killed by irradiation, mixed with live
responder lymphocytes from recipient. Mixture incubated in cell culture. DNA
synthesis measured by Tritiated Thymidine. Greater synthesis means donor and
recipient MHC not similar. unsatisfactory match
Cross matching
• Lysis of donor lymphocytes by addition of recipient
• serum due to preformed Cytotoxic antibodies.
ABO cross matching: of donor & recipient
• In siblings 25% chance for sharing both haplotypes, 50% for one haplotypes, 25%
for no haplotype

14. RESULTS OF ORGAN TRANSPLANT
• Well matched donor- recipient – chances of long term survival enhanced.
• 5 yr survival rate in two haplotype matched kidney transplant from related donor
was 95%. One haplotype matched 80%, from cadaver donor 60% ( higher if
recipient had many transfusions).
• Heart - 5 yr survival rate 50- 60%
• Liver - 5 yr survival rate less than 50%.
• Corneal graft successful. b/c it is avascular. Lymphatic supply prevents antigens
from triggering immune response. Only 1yr immunosupppression

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