- Increased activity in the field of organ transplantation initiated the accelerated study of human histocompatibility antigens, which are a part of HLA system. Histocompatibility differences between people are the result of differences at one major locus. The super locus of HLA system contains a large’number of genes related to immune system functions in human being.This gene resides on short arm of chromosome number 6 and encodes cell surface antigens presenting proteins and has many other functions.
- HLA genes are human version of genes that are present in most of the vertebrates. As HLA locus is responsible for production of many antigens, it is highly unlikely that any two unrelated individuals will be identical at this locus. Hence it is apparently clear that unrelated individuals would rarely be compatible to accept grafts from each other without any danger or rejection. Greater the similarities at this locus, the more likely it is that the graft will be accepted/ the transplant will not be rejected.
• Causes of Individual Variability in HLA System
- A refined recognition process which may act as surveillance within the body for mutant cells displaying changes in surface antigens.
- Defence against neoplasia by elimination of the altered/ mutant cells.
• Functions of HLA System
- (1) Proteins encoded by HLA are unique to every person. They are present on outer part of body cells.
- (2) The immune system uses these antigens/ proteins to differentiate self-cells and non-self-cells. This results in rejection of graft when there is difference in HLA system of acceptor and donor.
- (3) In Infectious Diseases : Presenting of foreign antigen to T-cells which kill the foreign antigen.
- (4) Autoimmunity : Certain HLA antigens are associated with some autoimmune disorders like type 1 diabetes, ankylosing spondylitis, systemic lupus erythematous etc.
- (5) In Cancer:- HLA mediated diseases are directly involved in the promotion of cancer. Eg. Gluten- sensitive enteropathy is associated with T-cell lymphoma.
Alleles
- A,B,C,D,Dr.-loci 17 ,29 ,7 ,11, 7-Number of alleles
- Generates enormous no. of haplotypes
- Broadly 3 groups of alleles
- (1) A2:- Frequently high in all populations
- (2) A1:- Present in all populations but high in certain populations eg. Africans
- (3) BW42:- confined to some populations such as Africans