8536d_cho7 161-184 8/16/02 12: 09 PM Page 169 mac100 mac 100: 1?/8_tm: 8536d: Goldsby et al./Immunology Se Major Histocompatibility Complex CHAPTER 7 Tn CC mRNA mRNA LILLA a chain B chain Class I MHC Class II MHC nolecule B? COOH HN→S DDDyCCOOH H2N H2N mRNA L al (2 TmcC m+C FIGURE7-9Schematic diagram of(a)class I and(b)class l MHC codes a separate domain of the MHC molecule. The leader peptides genes, mRNA transcripts, and protein molecules. There is corre- are removed in a post-translational reaction before the molecules are spondence between exons and the domains in the gene products; expressed on the cell surface. The gene encoding B2-microglobulin is note that the mRNA transcripts are spliced to remove the intron se. located on a different chromosome. Tm=transmembrane; C uences. Each exon, with the exception of the leader(L)exon, en- cytoplasmic followed by five or six exons encoding the a chain of the class Class I and ll Molecules Exhibit I molecule(see Figure 7-9a). The signal peptide serves to fa- Polymorphism in the Region That cilitate insertion of the a chain into the endoplasmic reticu lum and is removed by proteolytic enzymes in the Binds to Peptides ndoplasmic reticulum after translation is completed. The Several hundred different allelic variants of class I and II MHC ext three exons encode the extracellular al, a 2, and a3 do- molecules have been identified in humans. Any one individual, mains, and the following downstream exon encodes the however, expresses only a small number of these molecules transmembrane(Tm)region; finally, one or two 3-terminal up to 6 different class I molecules and up to 12 different class ll exons encode the cytoplasmic domains(C) lecules. Yet this limited number of mhc molecules must be Like class I MHC genes, the class II genes are organized able to present an enormous array of different antigenic pep- into a series of exons and introns mirroring the domain struc- tides to T cells, permitting the immune system to respond ture of the a and B chains(see Figure 7-9b) Both the a and specifically to a wide variety of antigenic challenges. Thus, pep- the B genes encoding mouse and human class II MHC mole- tide binding by class I and ll molecules does not exhibit the fine cules have a leader exon, an al or Bl exon, an a2 or B2 exon, specificity characteristic of antigen binding by antibodies and a transmembrane exon, and one or more cytoplasmic exons. T-cell receptors. Instead, a given MHC molecule can bindfollowed by five or six exons encoding the chain of the class I molecule (see Figure 7-9a). The signal peptide serves to fa￾cilitate insertion of the chain into the endoplasmic reticu￾lum and is removed by proteolytic enzymes in the endoplasmic reticulum after translation is completed. The next three exons encode the extracellular 1, 2, and 3 do￾mains, and the following downstream exon encodes the transmembrane (Tm) region; finally, one or two 3-terminal exons encode the cytoplasmic domains (C). Like class I MHC genes, the class II genes are organized into a series of exons and introns mirroring the domain struc￾ture of the and  chains (see Figure 7-9b). Both the and the  genes encoding mouse and human class II MHC mole￾cules have a leader exon, an 1 or 1 exon, an 2 or 2 exon, a transmembrane exon, and one or more cytoplasmic exons. Class I and II Molecules Exhibit Polymorphism in the Region That Binds to Peptides Several hundred different allelic variants of class I and II MHC molecules have been identified in humans. Any one individual, however, expresses only a small number of these molecules— up to 6 different class I molecules and up to 12 different class II molecules.Yet this limited number of MHC molecules must be able to present an enormous array of different antigenic pep￾tides to T cells, permitting the immune system to respond specifically to a wide variety of antigenic challenges. Thus, pep￾tide binding by class I and II molecules does not exhibit the fine specificity characteristic of antigen binding by antibodies and T-cell receptors. Instead, a given MHC molecule can bind Major Histocompatibility Complex CHAPTER 7 169 DNA 5′ 3′ α1 α2 α3 Tm C C (a) COOH H2N α chain DNA 5′ 3′ β1 β2 CC Tm+C (b) Class I MHC molecule mRNA mRNA mRNA (A)n (A)n (A)n DNA 5′ 3′ α1 α2 α1 α2 Tm+C C S S S S S S L α1 α2 α1 α3 β2 - microglobulin L CC α2 α3 Tm L C β1 β2 C L L Tm+C L C Tm+C COOH COOH H2N H2N β chain α chain Class II MHC molecule S S S S S S β1 β2 α1 α2 FIGURE 7-9 Schematic diagram of (a) class I and (b) class II MHC genes, mRNA transcripts, and protein molecules. There is corre￾spondence between exons and the domains in the gene products; note that the mRNA transcripts are spliced to remove the intron se￾quences. Each exon, with the exception of the leader (L) exon, en￾codes a separate domain of the MHC molecule. The leader peptides are removed in a post-translational reaction before the molecules are expressed on the cell surface. The gene encoding 2-microglobulin is located on a different chromosome. Tm  transmembrane; C  cytoplasmic. 8536d_ch07_161-184 8/16/02 12:09 PM Page 169 mac100 mac 100: 1268_tm:8536d:Goldsby et al. / Immunology 5e-: