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Bi1_2009_Lecture22_full

Bi1_2009_Lecture22_full - Clicker question Antibodies...

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Clicker question Antibodies against foreign MHC molecules can be isolated from the blood of transplantation patients and multiparous women (women who have had more than one baby). Which portion of the MHC molecule are the antibodies likely to recognize? Polymorphic Less polymorphic or non-polymorphic 1) The bound peptide 2) Residues in the polymorphic top half of the protein 3) The non-polymorphic membrane-proximal domains
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Clicker question Diversity results from combinatorial joining of gene segments and somatic mutation (not germline encoded): ___________ Diversity results from combinatorial joining of gene segments (not germline encoded): _____________ Diversity results from inheritance of different alleles (germline encoded): ______________ 1) T cell receptors, MHC, antibodies 2) MHC, antibodies, T cell receptors 3) Antibodies, T cell receptors, MHC 4) T cell receptors, antibodies, MHC 5) MHC, T cell receptors, antibodies 6) Antibodies, MHC, T cell receptors
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T cell co-receptors CD8 binds to MHC class I proteins. CD8 T cells are cytotoxic T lymphocytes (CTLs) or killer T cells. CD4 binds to MHC class II proteins. CD4 T cells are “helper” T cells. Two distinct functions of T cell co-receptors: Adhesion molecules - bind to appropriate MHC molecule (class I versus class II) on antigen presenting cell or infected cell and increase efficiency of antigen recognition Signaling molecules - transduce signal as part of activation pathway
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Clicker question CD4 and CD8 bind to class II and class I MHC molecules, respectively. Which part of an MHC/ peptide complex are they likely to recognize? 1) The bound peptide 2) The ± -helices on the peptide binding groove 3) The non-polymorphic membrane-proximal domains Polymorphic Less polymorphic or non-polymorphic
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Unlike T cell receptors, CD4 and CD8 do NOT recognize peptides bound to MHC proteins Both co-receptors bind to a non-polymorphic region of an MHC protein distant from the peptide-binding site. CD4 binds to ALL class II MHC/peptide complexes. CD8 binds to ALL class I MHC/peptide complexes
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Model for TCR/classI/ peptide/CD8 complex CD8 ± CD8 ² Class I ± 1, ± 2, ± 3 ² 2m TCR V ± TCR V ² From Gao et al., 1997, Nature 387, 630-634. T cell Target cell A T cell receptor (TCR) and a T cell co-receptor bind simultaneously to the same MHC/peptide complex
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Model of CD4 and T cell receptor binding to a class II MHC/ peptide complex Wang et al., 2001, PNAS 98, 10799-10804 Class II MHC T cell receptor CD4 T cell Antigen presenting cell
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Kwong et al., 1998, Nature 393: 648-659 CD4 also binds to HIV gp120, a component of the trimeric HIV envelope spike. This is a crystal structure of gp120 bound to CD4 and a Fab from an anti-gp120 antibody. All current crystal structures are of monomeric gp120.
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Which is true?
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