Chap 8 MHC and Ag Presentation PDF

Chap 8 MHC and Ag presentation MHC and transplantation MHC structure MHC polymorphism Ag presentation: MHC class I endogenous Ag Tc (CD8) MHC class II exogenous Ag Th (CD4) cross presentation MHC and Graft More MHC diversity, More tolerant of Grafts. The host will not r...

Chap 8 MHC and Ag presentation MHC and transplantation MHC structure MHC polymorphism Ag presentation: MHC class I endogenous Ag Tc (CD8) MHC class II exogenous Ag Th (CD4) cross presentation MHC and Graft More MHC diversity, More tolerant of Grafts. The host will not reject “things” (MHC) that it has Self-MHC Restriction Zinkernagel & Doherty: Nobel Prize 1997 A T cell recognizes Ag presented in the context of self MHC. True for both CD8 and CD4 Different T cells interacts with different MHC classes Th – CD4 – MHC II Tc – CD8 – MHC I MHC + Ag interacts with TCR MHC Structure  MHC binding of peptide Class I 9 a.a Class II 13-18 a.a Peptide consensus for class I NEJM Sep 7,  MHC structures and peptide biding β FIGURE 8.3. Different depictions of MHC class I molecule. (A) Cartoon of an MHC class I molecule associated at the cell surface with β2m. (B) Side view of MHC class I molecule with β2m, showing peptide-binding groove. (C) Top view of peptide-binding groove, showing bound peptide. (D) Diagram of interaction of T-cell receptor with MHC class I molecule and peptide bound in peptide-binding groove. (Parts B and C adapted from Bjorkman et al., 1987, with permission; part D adapted from Rammensee et al., 1993.) Diversity in MHC Multiple genes (3 loci for MHC I and 3x2 for MHC II) Large number of polymorphism (>100 each in population) Paternal and maternal alleles Group exercise How many different MHC I do each person express if they are heterozygous at all loci? How many different MHC II do each person express if they are heterozygous at all loci? MHC II distribution Almost all nucleated cells express MHC I Only specialized cells express both class I and II Processing of exogenous antigen in MHC class II pathway Processing of endogenous antigen in MHC class I pathway. Selective binding of peptides to MHC TAP Transporters Associated w/ Ag Processing  Class I and II pathways http://www. youtube.com/ watch?v=dw73 PzjgGJA&featur e=related – class II http://www. youtube.com/ watch?v=9bLf CnZLRN0&fe ature=related – class I ▪ Notice the differences Source of Ag? when peptides are loaded?  Cross presentation ▪ DC are not infected by most viruses ▪ Therefore DC in theory can’t present peptides to Tc cells via class I MHC ▪ Cross presentation becomes handy Mostly in DC’s Class I presenting exogenous Ag ▪ Class II can also present endogenous Ag ▪ CD1 and CD1 recognizing Cells ▪ CD1 presentation of lipids ▪ CD1 resembles MHC I, has β2 microglobulin ▪ CD1abc – γδT cells ▪ CD1d- NKT Lipid Antigens and Superantigens Lipid antigens activate special cells CD1abc – γδT cells CD1d - NKT Superantigen Not presented by MHC Polyclonally activate many T cells Can cause shock