Major Histocompatibility Complex Notes

Major Histocompatibility Complex And Transplantation

The major histocompatibility complex (MHC) is a region of multiple expressed genes on chromosome 6 (6p21.3), the products of which are critical for immunologic specificity, histocompatibility, and in susceptibility to several autoimmune diseases.

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Many of these genes are essential for innate and adaptive immunity. Since these genes were first identified on the surface of leucocytes, it is also called as human leucocyte antigen (HLA) region.

• HLA region has high polymorphism and thus there are many alleles of MHC genes, which pose a major challenge for donor-recipient matching (histocompatibility) in tissue transplantation.
• Most MHC genes or transplantation antigens on the short arm (p) of chromosome 6 occupy four regions or loci — A, B, C and D, having marked variation in allelic genes at each locus.
• The letter w in some of the genes (for example., Dw3, Cw4, Bw15, etc) refers to the numbers allocated to them at international workshops.
• Depending upon the characteristics of MHC genes (or molecules or antigens), they have been divided into 3 classes

Class, 1 MHC genes:

Have loci as HLA-A, HLA-B, and HLA-C. T suppressor (CD8+) lymphocytes carry receptors for class I MHC and these cells are used to identify class I antigens on them although class I antigens are present on all nucleated cells and platelets.

The protein complex domain is constituted by α₁, α₂, and α₃ chains and β₂ microglobulin. They play a major role in graft rejection. Besides, these antigens play a role in the destruction of virus-infected cells and in the lysis of tumor cells.

Class 2 MHC genes:

Have a single locus as HLA-D. HLA-D has a further 3 loci: R, Q, and P, and hence three corresponding subregions HLA-DR, HLA-DQ, and HLA-DP.

Class II MHC antigens  Are identified on antigen-presenting cells (macrophages, dendritic cells) and activated B cells and T helper (CD4+) cells.

Class II protein complex domain is composed of α₁, α₂ chains and β₁ and β₂ chains. They play a significant role in graft versus host response and in immune reactions involving CD4+ cells.

Class 3 MHC genes:

Code for some components of the complement system (C2, C4) and cytokine TNF but are not associated with HLA expression and hence are not used in antigen identification.

Given the high polymorphism of class I and class II genes, they have several alleles on loci numbered serially like HLA-A 1, HLA-A 2, HLA-A 3, etc.

MHC antigens present on the cell surface help the macrophage in its function of recognition of bacterial antigen i.e. they help to recognize self from foreign, and accordingly present the foreign antigen to T cells (CD4+ or CD8+) or to B cells.

Role Of The Complex

The HLA complex is significant in several ways:

1. Organ transplantation:

Historically, the major importance of the HLA system is in matching donor and recipient for tissue transplantation.

The recipient’s immune system can recognize the histocompatibility antigens on the donor organ and accordingly accept it or reject it. Both humoral as well as cell-mediated immune responses are involved in the case of genetically nonidentical transplants.

2. Regulation of the immune system:

Class I and II histocompatibility antigens play a role in regulating innate and adaptive immunity:

• Class I MHC antigens regulate the function of cytotoxic T cells (CD8+ subpopulation) for example. In virus infections.
• Class II MHC antigens regulate the function of helper T cells (CD4+ subpopulation) for example, Graft versus host response helps in B cell function.

3. Susceptibility to diseases:

• An increasing number of diseases are found to have an association with HLA types, most often with MHC class II. A few examples include the following:
• Autoimmune disorders for example, Rheumatoid arthritis, celiac disease, Sjögren’s syndrome, SLE, Memphis vulgaris, chronic active hepatitis.
  ‘Spondyloarthropathies, for example, ankylosing spondylitis, Reiter’s syndrome.
• Endocrinopathies, for example, Type 1 diabetes mellitus.
  ‘Neurologic for example, Myasthenia gravis The mechanism of
• HLA association with diseases is complex and heterogeneous involving multiple steps causing activation of T cells and.

Comparative features of MHC class I and class II are summed up in Table

Major Histocompatibility Complex

HLA system or MHC is composed of antigenic proteins present on all nucleated cells of the body and platelets, but have been first detected on leucocytes.

• MHC or transplantation antigens are located on the short arm of chromosome 6 and have 4 regions or loci: A, B, C, and D.
  There are 3 classes of antigens.
• Class I antigens are located on CD8+ cells and have loci as HLA-A, HLA-B, and HLA-C. Class II antigens have a single locus, HLA-D which has further 3 subregions (R, Q, P), and hence corresponding subtypes as HLA-DR, HLA-DQ, and HLA-DP.
• These genes are identified in B cells and CD4+ cells. Class III MHC antigens code for components of complement and TNF but have no role in antigen identification.
• The main roles of the HLA complex are in organ transplantation and regulation of the immune system. Besides, susceptibility to many autoimmune diseases has been found with specific HLA types.