Lecture 6- T Cell Receptors & MHC Molecules Flashcards
Which immune cell recognition can:
- Directly recognize and bind antigens (solo fighters)
- Recognize diverse antigens
- Proteins, carbohydrates, lipids, nucleic acids
B cell recognition (BCR & antibody)
B cells are considered professional APCs
Which immune cell recognition can:
- ONLY recognize antigens when presented by MHC molecules
- MCH recognizes only peptide antigens (protein)
T cell recognition (TCR)
bcs MCH only recognizes peptide antigens, same goes for T cells, bcs they recognize MCH
What are accessory molecules?
Molecules (integral membrane proteins) that are necessary or merely augment the T-cell response to an antigen.
(they assist by enhancing cell-cell adhesion, transducing signals, and promoting activation.)
What are the 2 domains of the segment protruding from the membrane?
(α & ß OR y & δ (gamma & delta) chains)
- C domain: close to the membrane
- V domain: distant from the membrane
- 3 hypervariable regions, specific for antigen & MHC molecule
- Has the peptide binding groove in the V domain
95% alpha-beta
5% gamma-delta = may recognize carbohydrate antigens
Why would gamma-delta chains being able to recognize carbohydrates be significant?
because this indicates NO MHC restriction, and those TCRs are able to bind outside peptides/proteins
What are the TCR accessory molecules?
- CD4 (Helper T)
- CD8 (Cytotoxic T)
- CD3 complex
- Zeta-zeta dimer (greek symbol- ζ )
- LFA-1 (CD11)
(come back to slide 8 and make cards for individual molecules)
What is the function of CD4 and CD8?
To sense the MHC molecule that is attached to an antigen
(they are co-receptors)
What is the function of CD3 complex?
To transduce signals
(4 peptide chains
2 dimers = gamma-epsilon & delta-epsilon )
What is the function of zeta-zeta dimers (ζ-ζ )?
Aids in transcription & translation
(Have ITAMs → conveying signals to the interior of the T cell to the nucleus)
What is the function of LFA-1 (CD11)?
Integrin that docks the T cell to the APC
What are ITAMs?
Immunoreceptor tyrosine-based activating motifs
- activated by phosphorylation
- they are BCR and TCR accessory proteins, as well as other receptor proteins
- essential for signal transduction
y-delta (gamma-delta) T cells:
- mysterious
- Derived from a separate cell lineage
- (may be) first-line defense at epithelial tissues
- NOT MCH restricted
- (may) recognize carbohydrate antigens presented by CD1 molecules
(similar to MHC)
Does TCR perform class switching (replacement of heavy chain)?
No
Does a TCR perform somatic hypermutation/ affinity maturation?
No
What factors contribute to TCR diversity?
- Gene rearrangements
- Multiple V region genes
- random combinations of chains
- significant variations (1016-1018)
What factors contribute to BCR diversity?
- Gene rearrangement
- Class switching = replacement of heavy chain
- Somatic hypermutation = affinity maturation
What is MHC?
Major histocompatibility complex
- Area of the genome coding for a series of proteins expressed in the cells in the body
ake form of antigens [SELF-antigens] → human leukocyte antigens HLA
What are 2 features of HLA (human leukocyte antigens)?
- unique to every person
- Only monozygotic twins have identical HLA locus
What is HLA (human leukocyte antigens) responsible for?
graft rejection, or tissue compatibility
- Flags the immune system which allows the immune system to distinguish between the self-proteins/antigens vs non-self-proteins/antigens
Why do T-cells interact with MCH molecules/proteins?
to determine if the material contacted belongs in the body
- if the material is recognized as harmful, both the material and APC are destroyed
What do MCH molecules do?
They recognize protein antigens and present them to T cells through APCs
( antigens include both self-proteins and foreign proteins produced within the cells [ex: viral proteins that take over the cell’s machinery in order to replicate the virus] )
On what cells is MCH class 1 found?
All nucleated cells
What are some features of MCH 1?
- heterodimer: α and ß chains
- presents peptides of about 8-11 amino acids
- presents endogenous (intracellular) peptides
- Presents about 8-11 amino acids → binds to smaller-sized peptides
- The peptide binding groove is located in the ALPHA chain
What does MCH 1 present?
- Self-antigens/proteins
- Foreign proteins produced within the cell → Viral proteins that take over the host cells & replicate the virus
- Present antigen to cytotoxic T cell lymphocyte [CD8 cells]
- Bind to CD8 adhesion molecules on
What are some features of MCH 2?
- Heterodimers = α & ß chains
BOTH chains insert into the cell membrane
BOTH chains have the peptide binding groove
-Present exogenous peptides to T helper cells
What 2 methods do helper T-cells use to bind and function?
- Binding to macrophages or dendritic cells w/ MHC 2-antigen → T helper cell activated to release lymphokines that attract other cells to the infection area
- Binding to B cell MHC 2-antigen → T helper cell stimulates B cells to develop clones of antibody-producing cells against the antigen material
What is the difference between the chains of MCH 1 and 2?
MCH 1- ß chain does not insert into the cell membrane, the peptide binding groove is in α chain
MCH 2- BOTH chains insert into the cell membrane, peptide binding groove is located in BOTH chains
On what 3 cells is MCH class 2 found?
- B cells
- Macrophages
- Dendritic cells
(professional APCs)
T cells are specific for both ___ and ___ molecules
anitgen; MCH
When can a T cell react?
this question sucks so idk if it will stay
only with its specific antigen if it is presented by a ‘self’ MCH molecule
When is TCR interaction with self MCH learned?
in the thymus during T-cell development
( - From positive selection & negative selection
- Checkpoints during Double Positive that simplify the T cell into Single Positive)
What contributes to antibody diversity?
- gene rearrqangement
- somatic hypermutation (affinity maturation)
- class switching
What contributes to TCR/BCR diversity?
gene rearrangement
What contributes to RAG-1/2 diverstiy?
Operate during gene rearrangement in BOTH T and B cells
(This initiates the VDJ rearrangement of the heavy chain [B cell] & the beta chain [T cell])
What contributes to MHC diverstity?
polymorphism
