Lecture 12 Flashcards
(25 cards)
What is the structure of the Tcell receptor??
one alpha chain + one beta chain
Both with variable and constant regions
How does TCR compare to antibody structure and function?
Specific for antigenic determinant
They recognize antigen in conjunction with MHC molecules on surface of APC’s
How do TCR see antigens?
Broken down into small fragments in APC’s
Then are places on MHC molecules, which are presented on the cell surface of APC
So they see the peptide in the context of the MHC molecule
What is the purpose of the T cell receptor?
TCR complex ( TCR +CD3) binds to the MHC peptide complex with VARIABLE region & signaling thru CD3
What its he purpose of TCR co receptor?
Where is CD4 andCD8 found?
CD4 or CD8 coreceptor helps TCR bind to the MHC for longer periods of time
CD4 is on helper T cells and binds to MHC class2
CD8 is on cytotoxic T cells and binds to MHC class1
Where do T cells come from and where do they develope?
Come from bone marrow, develope in the thymus to become mature
What are markers that define the developmental stages of thymocytes?
What are the stages of maturity??
Maturity is defined by presence of coreceptors
Most immature are DN & do not express co receptors
Intermediate DP, express both CD4 and CD8
Mature express only one SP
Once they are mature, where do they reside?
SP, only express one co receipt and found within the blood and in secondary lymphoid organs (lymph nodes, spleen)
What’s pos selection?
In the thymus, Tcells learn self MHC
If it recognizes self MHC at moderate affinity— TCR aB rearrangement is complete and becomes mature SP cells
SP cell leaves the thymus
What is negative selection?
If a T cells recognizes self MHC with strong affinity, dies via apoptosis
What is the ultimate goal of T cells recognizes developement?
Self MHC restricted recognize foreign antigens with self MHC
Self tolerance not to respond to self peptides
Cell types controlling T cell development ?
Thymic epithelial cells
Dendritic cells and macrophages
Characteristics of MHC genes?
Extensive polymorphism — in antigen binding sites
Polygyny and co dom expression
* heterodimer w 2 subunits
How does DN rearrange in T cells?
DN—> B chain arrange — A chain arrange —> DP—> SP
What is MHC?
Major histocompatibiity complex
Molecules that define self vs non self interactions
What is MHC class 1?
What is the structure like?
What are the classes?
Present in all cells of body except RBc, they lack nuclei and present intracellular antigens to CD8
One a chain,
3 globular regions wth B2m,
a 1 and a2 are variable domains that make up the binding cleft
Binds short peptides by both ends
What are the classes of MHC 1 that is binds?
HLA A, B,C , E,F,G
ABC— involved in antigen presentation
EG— prevent killing by NK cells
MHC and peptide is based on H bonds, van der walls, and hydrophobic interactions
What is MHC 2?
What is the structure like?
Present on professional APC— like dendritic , macrophages and B cells
Presence defines that it can present to helper T cells
A and B chains with globular domains— A1 and B1 form the antigen binding site
Length of peptide not constrained
What ae the MHC class 2?
HLA DR, DQ, DP, DM, DO
DR, DQ, DP on cell surface
DM and DO involved in processing of antigens
How does MHC intheritant compare to that of B and TCR?
MHC genes do not rearrange
Expressed as encoded in the germline
Different alleles are inherited from both parents & expression is codominant, which allows for several different MHC sequences to be expressed
What are HLA and halo type and what contributes to HLA diversity in humans?
Another term of MHC
Halo type is combination of MHC alleles
Humans contain many different MNHC due to polymorphism which diversifies HLA types
What are major function of MHC?
Presenting self antigens to developing thymocytes to support their development &shape the mature T cell in the thymus
Presenting foreign antigens to T cells to activate them in the periphery
What are sim and Diff between expression of BCR and TCR?
Sim:
use VDJ genes
Need RAG 1/2
Allelic exclusion
Diff:
TCR does not secrete product with same binding site as receptors
TCR constant regions don’t determine function
TCR does not undergo somatic hyper mutation
What are the sim and diff between BCR (Ig) and TCR?
Receptor, antigenic determinants , diversity, MHCrestrict, antigen, antigen processing?
BCR has soulube or membrane bound
TCR is membrane
In variable regions
Millions of different speficities
TCR: yes, BCR: none
BCR: native protein , TCR: MHC
BCR: no processing , TCR: yes