The MHC Encodes Three Major Classes of Molecules

The major histocompatibility complex is a collection of genes arrayed within a long continuous stretch of DNA on chromosome 6 in humans and on chromosome 17 in mice. The MHC is referred to as the HLA complex in humans and as the H-2 complex in mice. Although the arrangement of genes is somewhat different, in both cases the MHC genes are organized into regions encoding three classes of molecules (Figure 7-1):

■ Class I MHC genes encode glycoproteins expressed on the surface of nearly all nucleated cells; the major function of the class I gene products is presentation of peptide antigens to TC cells.

VISUALIZING CONCEPTS

Mouse H-2 complex

Complex

H-2

MHC class

I

II

III

I

Region

K

IA

IE

S

D

Gene products

H-2K

IA ap

IE ap

C' proteins

TNF-a TNF-P

H-2D

H-2L

Human HLA complex

Complex

HLA

MHC class

II

III

I

Region

DP

DQ

DR

C4, C2, BF

B

C

A

Gene products

DP ap

DQ ap

DR ap

C' proteins

TNF-a TNF-p

HLA-B

HLA-C

Simplified organization of the major histocompatibility complex (MHC) in the mouse and human. The MHC is referred to as the H-2 complex in mice and as the HLA complex in humans. In both species the MHC is organized into a number of regions encoding class I (pink), class II (blue), and class III

(green) gene products. The class I and class II gene products shown in this figure are considered to be the classical MHC molecules. The class III gene products include complement (C') proteins and the tumor necrosis factors (TNF-a and TNF-P).

■ Class II MHC genes encode glycoproteins expressed primarily on antigen-presenting cells (macrophages, dendritic cells, and B cells), where they present processed antigenic peptides to TH cells.

■ Class III MHC genes encode, in addition to other products, various secreted proteins that have immune functions, including components of the complement system and molecules involved in inflammation.

Class I MHC molecules encoded by the K and D regions in mice and by the A, B, and C loci in humans were the first discovered, and they are expressed in the widest range of cell types. These are referred to as classical class I molecules. Additional genes or groups of genes within the H-2 or HLA complexes also encode class I molecules; these genes are designated nonclassical class I genes. Expression of the non-classical gene products is limited to certain specific cell types. Although functions are not known for all of these gene products, some may have highly specialized roles in immunity. For example, the expression of the class I HLA-G molecules on cytotrophoblasts at the fetal-maternal interface has been implicated in protection of the fetus from being recognized as foreign (this may occur when paternal antigens begin to appear) and from being rejected by maternal TC cells.

The two chains of the class II MHC molecules are encoded by the IA and IE regions in mice and by the DP, DQ, and DR regions in humans. The terminology is somewhat confusing, since the D region in mice encodes class I MHC molecules, whereas the D region (DR, DQ, DP) in humans refers to genes encoding class II MHC molecules! Fortunately, the designation D for the general chromosomal location encoding the human class II molecules is seldom used today; the sequence of the entire MHC region is available so the more imprecise reference to region is seldom necessary. As with the class I loci, additional class II molecules encoded within this region have specialized functions in the immune process.

The class I and class II MHC molecules have common structural features and both have roles in antigen processing. By contrast, the class III MHC region, which is flanked by the class I and II regions, encodes molecules that are critical to immune function but have little in common with class I or II molecules. Class III products include the complement components C4, C2, BF (see Chapter 13), and inflammatory cytokines, including tumor necrosis factor (TNF) and heat-shock proteins (see Chapter 12).

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Responses

  • keke tiilikainen
    Is expressed on the MHC III REGION?
    8 years ago
  • michael
    What encodes for mhc heavy chain?
    10 months ago

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