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Chapter 7. ANTIGEN-PRESENTING CELLS

So-called Human Leukocyte Antigens (HLA) are glycoproteins encoded by genes of Major Histocompatibility Complex (MHC), they determine biologic individuality of each human being. In immune system these glycoproteins perform a very important function: they take part in peptide antigen presentation to T-lymphocytes by antigen-presenting cells (APC).

MAJOR HISTOCOMPATIBILITY COMPLEX

HLA-molecules encoded by MHC-genes are subdivided into glycoproteins of class I MHC (HLA-A, HLA-B, and HLA-C; these glycoproteins are presented on the surface of all somatic cells excluding the extravillous trophoblast cells and erythrocytes) and class II MHC (HLA-DP, HLA-DQ, and HLA-DR; they are predominantly expressed on membranes of the following APC - DC, activated macrophages, and B-lymphocytes as well as T-helper cells; non-immunocompetent somatic cells do not normally express MHC-II molecules. Ag-recognizing molecules of T-lymphocytes (at least TCRap) are able to "see" and bind Ag only in complex with MHC-I or MHC-II molecules, including those located on cell surface of the own organism. Hence a natural function of MHC proteins is to present Ag peptides to T-lymphocytes.

Genes of MHC complex

The MHC complex is very substantial in size and comprises some 2 000 allelic variants of genes. Genomic structure of the human MHC loci is shown in Fig. 7.1.

• MHC-I. Genes of the following groups: HLA-A, HLA-B and HLA-C

encode class I MHC molecules.

• MHC-II. Genes of the following groups: HLA-DP, HLA-DQ and HLA-DR encode class II MHC molecules.

• MHC-III. The term "MHC-III" designates the region located between MHC-I and MHC-II; the genes encoding certain components of complement system (C4a and C4b, C2, factor B), cytokines (TNF-a and lymphotoxin), and 21-hydroxylase (enzyme involved in biosynthesis of steroid hormones), etc., are mapped there.

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