HLA (human leukocyte antigen) is the expression product of human major histocompatibility complex (MHC Tetramer), which is the most complex polymorphic system known in the human body. Since the discovery of Jean Dausset's first HLA antigen in 1958, by the 1970s, HLA has become an important emerging field of research in immunogenetics, immunobiology and biochemistry. Now, the composition, structure and function of its system have been basically clarified, and its physical and chemical properties and biological effects have been clarified. These research results not only have important theoretical significance, but also have great biomedical value.
Nature and structure
HLA is a highly polymorphic allogeneic antigen whose chemical nature is a glycoprotein composed of an alpha heavy chain (glycosylated) and a beta light chain non-covalently bound. The amino terminus of the peptide chain is outward (about 3/4 of the entire molecule), the carboxyl terminus penetrates into the cytoplasm, and the intermediate hydrophobic portion is in the cell membrane. HLA is classified into class I antigens and class II antigens according to their distribution and function.
Genetic control
HLA is a gene cluster encoding the major histocompatibility complex (MHC) of humans. HLA is located on the short arm of chromosome 6.
The specificity of the HLAI-like antigen depends on the alpha heavy chain and is encoded by the HLA-A, B, and C sites; its beta light chain is β2-microglobulin, and the coding gene is on chromosome 15. The HLA class II antigen is controlled by the HLA-D region (including 5 sub-regions), and the A gene and the B gene are encoded by the α heavy chain and the β light chain, respectively, and the antigen polymorphism depends on the β light chain. Each of the above genes (named WHO nomenclature committee revised in 1975) is a polymorphic site (reciprocal) and codominant. If MHC is viewed as a whole, its polymorphism is more prominent. It is conservatively estimated that there are at least 1300 different haplotypes, correspondingly about 17 x 10 seven-squares genotype. This is the genetic basis of almost no HLA except for the identical twins, so that HLA can be regarded as an individual's "identity card."
Biological functions
Target function
HLAI-like antigens are distributed in all nucleated cells. Its antigen specificity lies in the specific amino acid sequence of the peptide chain epitope. These antigens can be altered by foreign substances such as certain viruses or chemicals. When these gene products are altered, they become autoimmune and become targets for immune exclusion. It can be seen that the essence of the target function is to "recognize the self" to ensure the integrity of the body. Therefore, it is important to distribute all cells and their polymorphisms.
Identification function
The recognition function of HLA refers to the unique synergy in the immune response. Antibodies are produced in B cells, but in most cases, macrophages and T lymphocytes are required to participate. The process is: after the antigen is processed by the macrophage, the antigen information is transmitted to the T helper cell, and the latter transmits the information to the B cell, so that the B cell further differentiates to generate a specific antibody. In this process, T helper cells not only recognize antigens on sensitized macrophages, but also recognize whether macrophages are consistent with their own class II antigens. That is to say, only when the haplotype of the macrophage and the haplotype of the T helper cell are identical, the T helper cell is activated, so that the immune response is carried out under strict genetic control.
Medical value
Organ transplantation
The HLA study was originally carried out under the auspices of organ transplantation research.
Therefore, HLA is also called transplant antigen. Clinical practice has shown that rejection of allogeneic transplants (except for identical twins) should be the biggest obstacle to success. In genetics, MHC is transmitted as a unit of Mendelian. Therefore, there may be three cases in which HLAs are identical, semi-identical, and different. Practice has proved that more than 90% of the kidney transplants of the same sibling donors with HLA have a good effect; the donors with different haplotypes have a significant effect; those with different phenotypes rarely survive. The revealing of the nature and function of HLA provides an important theoretical basis for transplantation matching. It can be said that organ transplantation is an important achievement in contemporary medicine.
A genetic marker for certain diseases
In 1972, Russel first reported that patients with psoriasis (psoriasis) carry HLA-B13 or HLA-B17. Since then, a large number of other diseases have been found to be associated with specific HLA. Among them, HLA-B27 antigen is found in about 90% of patients with ankylosing spondylitis, so that HLA typing has diagnostic value, and even the disease subtype can be confirmed earlier. Clinical differences, for example, psoriasis vulgaris is associated with HLA, whereas pustular psoriasis is not; juvenile insulin-dependent diabetes mellitus is associated with HLA-B8, HLA-Bw15, and HLA-B18, and late-onset diabetes There is no such correlation. Therefore, certain types of HLA are the genetic markers of certain diseases. For example, autosomal recessive adrenal hyperplasia is due to a lack of 21-hydroxylase. HLA antigen polymorphism was used for population association analysis and family linkage analysis. It was found that two hydroxylase sites (21-OHA and 21-OHB) were closely linked to HLA-B and DR. Accordingly, prenatal diagnosis can be made using HLA. In eugenics, the relative risk of a child's illness can be estimated for certain diseases based on available data. On the other hand, the relationship between HLA and longevity also forms a research hotspot.
Forensic
Because of its high polymorphism, HLA is the most representative genetic marker that is representative of individual specificity and is associated with the life of the individual. The HLA type has the same probability of being identical among the unrelated individuals. Forensic medicine uses HLA genotype or phenotype detection for individual identification to "identify the body", and because of its haplotype genetic characteristics, it is also an important means of paternity testing.
High resolution technology
With the development of medicine, such as leukemia, thalassemia, etc. can be typed and tested with the latest genetic technology, and then find a suitable donor for transplantation. At present, HLA high-resolution peripheral blood stem cell transplantation technology can greatly improve the matching effect, making the patient's recovery faster and more assured.
The latest HLA high-resolution typing technology makes it possible to establish a high-resolution HLA database, which not only helps to find suitable donors quickly and accurately, but also greatly improves the utilization rate of the bone marrow bank, making it better for patients, and can be HLA. Scientific research and technological innovation provide basic data support.
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