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Ag & T cells
Mathew - 1 hr
9
Medical
Graduate
04/05/2011

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Term
Basic structure of TCR and MHC molecules
Definition
TCR resembles a membrane-bound Fab; a heterodimer composed of an alpha and beta chain (or gamma and delta)
-EC portion has two Ig-like domains: one V-like, one C-like
-a member of the Ig superfamily
-both alpha & beta chains span the cell membrane, have short cytoplasmic tails
-heterodimer is associated with CD3 complex (gamma, delta, epsilon), and zeta. This complex does the signaling
-the cytoplasmic domains of CD3 proteins contain ITAMs, allow them to associate with protein tyr K (PTK)
-CD3 also req'd for expression of TCR on cell surface

MHC complex: region encoding MHC molec & other pr involved in Ag processing & presentation; causes T cells to reject transplants
-human MHC is called human leukocyte antigen (HLA); murine MHC is called histocompatibility-2
Term
Organization of MHC
Definition
4000 kb, on csome 6

class II region contains TAP1 & TAP2 genes (transporters in antigen processing) & LMP genes that encode proteosome subunits
-products of TAP1/2 --> protein pump, transports peptides from cytosol into ER where they can associate with MHCI H chains

Class III region separates I & II, contains complement genes

gene for beta-2 microglobulin *is not* on MHC (it's on csome 15)
Term
how polymorphism affects binding & presentation of peptide antigens to T cells
Definition
Polymorphism = variation at a single genetic locus and its product within a species

most of the polymorphic residues are located at the alpha1 & alpha2 domains of class I, and mainly the beta1 domain of class II, the domains that form the peptide binding cleft

affects Ag recognition indirectly by controlling peptide binding
Term
Understand the complex of peptide antigen and MHC molecule recognized by T cell receptor (TCR)
Definition
T cells recognize antigen ONLY in the presence of peptide bound to MHC on cell surface
Term
Antigen processing and presentation
Definition
-antigen processing: the breakdown of pathogen derived proteins into peptide fragments
-Ag presentation: assembly of peptides with MHC and display of these complexes on cell surface
Term
MHC-restriction of T cells
Definition
The recognition of an Ag by T cells is specific for the Ag as well as the MHC molecule that presents the Ag
-e.g. cytotoxic T cells isolated from a virally infected animal won't kill cells infected by the same virus from another animal of a different MHC haplotype
Term
TAP proteins
Definition
transport peptides from cytosol into ER

essential in MHC class I peptide loading
Term
MHC class I & II isotypes
Definition
I: HLA-A, HLA-B, HLA-C, HLA-E, HLA-F, HLA-G
-have an alpha or heavy chain and a non-MHC-encoded beta (beta2-microglobulin) chain
-alpha chain folds into alpha1, alpha2, alpha3. a1 & a2 form peptide binding cleft, can accommodate peptides of 9-11 AA
-A, B, C are "classical"

II: HLA-DP, HLA-DQ, HLA-DR, HLA-DM, HLA-DO
-are heterodimers of alpha and beta chains
-alpha1 & beta1 domains form peptide bonding region, can accommodate peptides of 10-30 AA
-DP, DQ, DR are "classical"
Term
Where are MHCI expressed?
On what cells are MHCII expressed?
Definition
B/c MHC is polymorphic most ppl are heterozygous at each locus
Class I molecules are expressed at all nucleated cells
Class II are normally only expressed on APC (B cells, macrophages, dendritic cells)
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