Self-Review: Going through the powerpoints for exam # 2 Flashcards
Class I Genes Humans
HLA-A; HLA-B; HLA-C
Class II genes Humans
HLA-DP; HLA-DQ; HLA-DR; TAP; HLA-DM
Class III genes Humans
Complement proteins (Factor b, C2, C4); Cytokines (TNF alpha, LT, LTb); TAP
Class I Genes Mice
H-2k, H-2D, H-2L
Class II genes Mice
I-A; I-E
What two factors contribute to diversity in MHC molecules?
Polymorphism and polygeny.
MHC haplotype
the particular set of alleles on a single chromosome
Where do peptide anchor residues bind to in MHC?
binding pockets in peptide binding groove; Polymorphisms in MHC molecules change the amino acids that line the peptide binding groove and change the pocket’s binding specificity
Where are the locations of the polymorphic residues in MHC I and MHC II respectively?
MHC I (a1 and a2); MHC II (a1 and b1)
Congenic mice
mice that are similar at all loci excepts the gene of interest
3 hypotheses to explain transition to single positive thymocytes
1) Stochastic model 2) Instructive model 3) Kinetic signaling model
Stochastic model
CD4 or CD8 is turned off randomly. No relation to TCR
Instructive model
TCR, CD8, MHC I leads to CD8+ differentiation
Kinetic Model
TCR, MHC II, CD4+ causes differentiation to CD4+ ; CD8 gets an interrupted signal survives with IL-7
DN1
CD44, Kit (reacts with SCF)
DN2
CD44, CD25 begin to rearrange b chain of TCR Db to Jb) become CD44 lo and Kit lo
DN3
CD44 lo, kit lo, CD25, continues to rearrange (Vb to DJb) and pair with preTa, CD3 begins to be expressed
DN4
CD44-, CD25-, Pre TCR w/CD3, allelic exclusion.
Alloreactivity
T cell react to differences in MHC from one animal to another (organ transplantation); another example is super antigens
Direct alloantigen recognition
T cell recognizes unprocessed allogeneic MHC molecule on graft APC
Indirect alloantigen recognition
Presentation of processed peptide of allogeneic MHC molecule bound to self MHC molecule
Super antigen
Superantigen binding to Class II MHC and TCR VB3; polyclonal activation of VB3+ T cells: cytokine storm and deletion of T cells.
For MHC I, what protein cleaves the carboxyl terminus of Peptides?
Proteosome
For MHC I, what protein cleaves the amino terminus of peptides?
ERAAP
Process of MHC binding
Class I is released from calnexin after b2m binds to MHC I, and is then bound by the complex cal reticulum, Erp57, and tapasin
Three ways antigens go from the phagsome to the cytosol.
1) phagsome degrades 2) retro-translocation through sec61- endoscope to ER 3) fusion of ER and phagosome
What is the purpose of positive and negative selection?
1) produce MHC restricted lymphocytes, 2) produce self tolerant lymphocytes
MHC restriction
Selecting for cells that recognize self MHC (positive selection )