8536d_cho7 161-184 8/16/02 12: 09 PM Page 162 mac100 mac 100: 1?/8_tm: 8536d: Goldsby et al./Immunology Se 162 PART II Generation of B-Cell and T-Cell Response VISUALIZING CONCEPTS Mouse H-2 complex III H-2K INF-a products B aB Cproteins TNFB/H-2DH-2L Human HLA complex HLA MHC class DP DQDR C4, C2, BF B C Gene DP DQ DR C'proteins TNF-CL BaBc阝 TNF-B HLA-BHLACHLA-A GURE7-1Simplified organization of the major histocompat- (green) gene products. The class I and class ll gene products bility complex(MHC)in the mouse and human. The MHC is re- shown in this figure are considered to be the classical MHC mol ferred to as the H-2 complex in mice and as the HLA complex in ecules. The class lll gene products include complement(C"pro- humans. In both species the MHC is organized into a number of teins and the tumor necrosis factors(TNF-a and TNF B) a Class II MHC genes encode glycoproteins expressed antigens begin to appear)and from being rejected by ma- nting cells(macrophages, ternal Tc cells dendritic cells, and B cells), where they present processed The two chains of the class li mhc molecules are en- antigenic peptides to TH cells coded by the la and ie regions in mice and by the DP, DQ and DR regions in humans. The terminology is somewhat a Class IlI MHC genes encode, in addition to other confusing, since the D region in mice encodes class I MHC products, various secreted proteins that have immune molecules, whereas the D region(DR, DQ, DP)in humans functions, including components of the complement refers to genes encoding class II MHC molecules! Fortu- system and molecules involved in inflammation nately, the designation D for the general chromosomal loca Class I MHC molecules encoded by the K and D regions in today; the sequence of the entire MHC region is available o tion encoding the human class II molecules is seldom used mice and by the A, B, and C loci in humans were the first the more imprecise reference to region is seldom necessary discovered, and they are expressed in the widest range of As with the class I loci, additional class II molecules en- cell types. These are referred to as classical class I molecules. coded within this region have specialized functions in the complexes also encode class I molecules; these gene.A immune process Additional genes or groups of genes within the H-2 or HLA The class I and class II MHC molecules have common designated nonclassical class I genes Expression of the non- structural features and both have roles in antigen processing classical gene products is limited to certain specific cell By contrast, the class Ill MHC region, which is flanked by the types. Although functions are not known for all of these class I and II regions, encodes molecules that are critical gene products, some may have highly specialized roles in immune function but have little in common with class I or II immunity. For example, the expression of the class I HLA- molecules. Class Ill products include the complement com- G molecules on cytotrophoblasts at the fetal-maternal in- ponents CA, C2, BF(see Chapter 13), and inflammatory cy terface has been implicated in protection of the fetus from tokines, including tumor necrosis factor (TNF)and being recognized as foreign(this may occur when paternal heat-shock proteins(see Chapter 12)■ 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 in￾terface 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 ma￾ternal TC cells. The two chains of the class II MHC molecules are en￾coded 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! Fortu￾nately, the designation D for the general chromosomal loca￾tion 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 en￾coded 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 com￾ponents C4, C2, BF (see Chapter 13), and inflammatory cy￾tokines, including tumor necrosis factor (TNF) and heat-shock proteins (see Chapter 12). 162 PART II Generation of B-Cell and T-Cell Responses VISUALIZING CONCEPTS FIGURE 7-1 Simplified organization of the major histocompat￾ibility complex (MHC) in the mouse and human. The MHC is re￾ferred 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 mol￾ecules. The class III gene products include complement (C) pro￾teins and the tumor necrosis factors (TNF- and TNF-). II III Complex MHC class Region Gene products IA αβ H–2K H–2L C′ proteins H–2D IE αβ TNF-α TNF-β TNF-α TNF-β H–2 I I K IA IE S D III Complex MHC class Region Gene products DQ αβ C′ proteins HLA-B HLA-C HLA-A DR αβ HLA II I DP DQ DR C4, C2, BF B C A Human HLA complex Mouse H-2 complex DP αβ 8536d_ch07_161-184 8/16/02 12:09 PM Page 162 mac100 mac 100: 1268_tm:8536d:Goldsby et al. / Immunology 5e-: