MAJOR HISTOCOMPATIBILITY COMPLEX

MAJOR HISTOCOMPATIBILTY COMPLEX:

M.H.C. molecules were discovered as products of genes that evoke rejection of transplanted organs.

· The physiologic function of mhc molecule ,is to display peptide fragments of proteins for recognition by antigen specific T-cells.

· M.H.C molecules are clustered on the chromosome 6,the MHC or the H.L.A. complex.

· The hla system is highly polymorphic.

Mainly there are two types of m.h.c. molecules.:-

· CLASS 1 M.H.C. MOLECULE

· CLASS 2 M.H.C. MOLECULE.

Class 1 m.h.c. molecules :-

· Class 1 M.H.C. molecules are expressed on all the nucleated cells and platelets,designated as HLA-A,HLA-B,HLA-C.

· Consists of three alpha subunits (α1,α2,α3) and a β-2.

· Crystal structure revealed that α-1 & α-2 domains form a cleft,or groove where the peptide binds.

Class 1 mhc molecules display peptides that are derived from proteins,such as viral antigens,that are located in the cytoplasm and usually produced in the cells,and class 1 associated proteins are recognized by CD8+ T lymphocytes.

The non-polymorphic α-3 domain of class 1 M.H.C. molecules has a binding site for CD8, and therefore the peptide class 1 complexes are recognized by CD8+ cells.

CLASS 2 M.H.C. MOLECULE:-

1. Class 2 M.H.C. molecules are encoded in a region called HLA-D,which has three sub regions HLA-DP,HLA-DQ,HLA-DR.

CLASS 2 M.H.C. molecules presents antigens that are internalized into vesicles ,and are typically derived from extracellular microbes and soluble proteins.

The class 2 β-2 domain has a binding site for CD4+ and therefore,the class 2 peptide complex is recognized by CD4+ cells which function as helper cells.

Class 2 M.H.C. molecules are mainly expressed on the cells that present ingested antigens and respond to T- cells help,(macrophages,b-lymphocytes,dendritic cells).

ANTIGEN PROSESSING:-

Class 1 M.H.C.:

1. In the class 1 M.H.C. pathway ,peptide are produced from proteins in the cytosol and transported to the endoplasmic reticulum(E.R),where they bind to class 1 mhc molecule.

2. the peptide M.H.C. complexes are transported to the cell surface and displayed for recognition by CD8+ T cells.

Class 2 M.H.C.:

· in the class 2 M.H.C. pathway, proteins are ingested into vescicles and degraded into peptides, which binds to class 2 M.H.C. molecules being transported in the same vescicles.

· The class 2 M.H.C. peptide complexes are expressed on the cell surface and recognized by CD4+ T cells.

Pushpendra singh

(2008-batch)

m.l.b. medical college

Jhansi (u.p.)