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Basics of HLA typing to prevent graft rejection | Immunology | Simplified explanation

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In this post, you'll learn about basics of :-

  • MHC antigens (HLA)
  • Graft rejection
  • HLA typing

Graft rejection


Image result for antigen
 Let's say you're going to perform renal transplantation for a patient who has renal failure. What's the first thing which will bother you and you'll be concerned about so much? Graft rejection right?

I know right. Even if everything goes well, there are always chances for graft rejection and one requires adequate immunosuppression to avoid such tragedy.

But before that, what are the factors which control graft rejection? Is there by any chance we can predict if a graft from a donor will be acceptable by the host's immune system? Fortunately, yes!

This is what is actually Histocompatibility.

Histocompatibility

Histocompatibility simply means the compatibility of donor's graft to the recipient's body. On making it simple, histocompatibility tells us if a graft from a donor will be suitable for the recipient. Will it be accepted or rejected by the recipient's immune system.

What are the various factors which determine histocompatibility?

Now imagine, you have only one friend initially for so many years. And one fine day, there comes a guy saying that he wants to join your gang. What will you do then? There are two possibilities.

  1. You accept his request and let him join your gang because you like his character and he's much of your type, or
Image result for friends cartoonImage result for enemies cartoon





        

       




2. You deny his friendship because you don't think he's a good guy or he's not of your type (or for any other reason)

The same thing happens after one receives a donor's graft.
The factors which decide the compatibility are called as transplantation antigens.

Most important of them is :-

  • Major histocompatibility complex (MHC) - You all would have definitely heard about this. They are the most important factor deciding the histocompatibility. The MHC antigens in humans are called as Human Leukocyte Antigens (HLA), because they were first observed on cell surface of leukocytes in humans. The HLA complex genes which code for MHC proteins are located in short arm of chromosome 6. The most important function of these MHC proteins is to bind peptide fragments of pathogens and they present it to T cells for destruction
So, how to prevent graft rejection? Before transplantation, it is necessary to carry out some lab tests.
- ABO and Rh blood compatibility testing between the donor and recipient
- HLA typing

HLA typing

Let me make this very simple. Donor's graft will have his HLA antigens. If the recipient already has antibodies against these kind of foreign HLA antigens, there will be hyperacute rejection of the graft very soon after transplantation.

Now how can this recipient already have antibodies against foreign HLA antigens? This recipient might have had previous blood transfusions or a prior organ transplantation in which cases, he might have developed these antibodies against foreign HLA antigens.

Detecting these antibodies against foreign HLA antigens in the recipient helps in determining histocompatibility to a great extent.

This can be done by a method known as HLA typing.

This test is very simple. Here we just check if the antigens on donor's leukocytes or if the HLA genes of donor matches with that of the recipient.

There are various methods to perform HLA typing. These are classified as :-

1) Phenotypic method :-

  • Serology (Microcytotoxicity)
  • Tissue typing (Mixed lymphocytic reaction)
2) Genotypic method :-

  • PCR (Polymerase Chain Reaction - detects HLA genes)
  • PCR-RFLP (Restriction Fragment Length Polymorphism)
  • VNTR typing (Variable Number Tandem Repeats)
  • STR typing (Short Tandem Repeats)
  • DNA Sequence based typing
  • Karyosome analysis


While it's not very important to know how these methods are performed, just remember that genotypic methods such as VNTR typing and DNA sequencing methods are more reliable and more commonly used these days compared to the phenotypic methods.

Hope you got some idea about MHC and HLA typing.

Thank you for reading! I'll see you in my next blog. BYE!

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