Lecture 6- T Cell Receptors & MHC Molecules

Question 1

Which immune cell recognition can:
- Directly recognize and bind antigens (solo fighters)
- Recognize diverse antigens
- Proteins, carbohydrates, lipids, nucleic acids

Answer 1

B cell recognition (BCR & antibody)

B cells are considered professional APCs

Question 2

Which immune cell recognition can:
- ONLY recognize antigens when presented by MHC molecules
- MCH recognizes only peptide antigens (protein)

Answer 2

T cell recognition (TCR)

bcs MCH only recognizes peptide antigens, same goes for T cells, bcs they recognize MCH

Question 3

What are accessory molecules?

Answer 3

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.)

Question 4

What are the 2 domains of the segment protruding from the membrane?
(α & ß OR y & δ (gamma & delta) chains)

Answer 4

• 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

Question 5

Why would gamma-delta chains being able to recognize carbohydrates be significant?

Answer 5

because this indicates NO MHC restriction, and those TCRs are able to bind outside peptides/proteins

Question 6

What are the TCR accessory molecules?

Answer 6

• 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)

Question 7

What is the function of CD4 and CD8?

Answer 7

To sense the MHC molecule that is attached to an antigen

(they are co-receptors)

Question 8

What is the function of CD3 complex?

Answer 8

To transduce signals

(4 peptide chains
2 dimers = gamma-epsilon & delta-epsilon )

Question 9

What is the function of zeta-zeta dimers (ζ-ζ )?

Answer 9

Aids in transcription & translation

(Have ITAMs → conveying signals to the interior of the T cell to the nucleus)

Question 10

What is the function of LFA-1 (CD11)?

Answer 10

Integrin that docks the T cell to the APC

Question 11

What are ITAMs?

Answer 11

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

Question 12

y-delta (gamma-delta) T cells:

Answer 12

• 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)

Question 13

Does TCR perform class switching (replacement of heavy chain)?

Answer 13

No

Question 14

Does a TCR perform somatic hypermutation/ affinity maturation?

Answer 14

No

Question 15

What factors contribute to TCR diversity?

Answer 15

• Gene rearrangements
• Multiple V region genes
• random combinations of chains
• significant variations (1016-1018)

Question 16

What factors contribute to BCR diversity?

Answer 16

• Gene rearrangement
• Class switching = replacement of heavy chain
• Somatic hypermutation = affinity maturation

Question 17

What is MHC?

Answer 17

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

Question 18

What are 2 features of HLA (human leukocyte antigens)?

Answer 18

• unique to every person
• Only monozygotic twins have identical HLA locus

Question 19

What is HLA (human leukocyte antigens) responsible for?

Answer 19

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

Question 20

Why do T-cells interact with MCH molecules/proteins?

Answer 20

to determine if the material contacted belongs in the body

• if the material is recognized as harmful, both the material and APC are destroyed

Question 21

What do MCH molecules do?

Answer 21

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] )

Question 22

On what cells is MCH class 1 found?

Answer 22

All nucleated cells

Question 23

What are some features of MCH 1?

Answer 23

• 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

Question 24

What does MCH 1 present?

Answer 24

• 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

Question 25

What are some features of MCH 2?

Answer 25

- 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

Question 26

What 2 methods do helper T-cells use to bind and function?

Answer 26

1. 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 2. Binding to B cell MHC 2-antigen → T helper cell stimulates B cells to develop clones of antibody-producing cells against the antigen material

Question 27

What is the difference between the chains of MCH 1 and 2?

Answer 27

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

Question 28

On what 3 cells is MCH class 2 found?

Answer 28

- B cells - Macrophages - Dendritic cells | (professional APCs)

Question 29

T cells are specific for both ___ and ___ molecules

Answer 29

anitgen; MCH

Question 30

When can a T cell react? | this question sucks so idk if it will stay

Answer 30

only with its specific antigen if it is presented by a 'self' MCH molecule

Question 31

When is TCR interaction with self MCH learned?

Answer 31

in the thymus during T-cell development ( - From positive selection & negative selection - Checkpoints during Double Positive that simplify the T cell into Single Positive)

Question 32

What contributes to antibody diversity?

Answer 32

- gene rearrqangement - somatic hypermutation (affinity maturation) - class switching

Question 33

What contributes to TCR/BCR diversity?

Answer 33

gene rearrangement

Question 34

What contributes to RAG-1/2 diverstiy?

Answer 34

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])

Question 35

What contributes to MHC diverstity?

Answer 35

polymorphism